HX641 25211 
RC343  .K14  Serology  of  nervous 


RECAP 


in 

H 
I 

1 

ififfiiil                    iiiiliilllllllll                                1            !         1 P    1     II                      ml 

llllllilllllllllli          lllllllllllllllliilllll llll  lllllillllll Ill  II  till!  1   1  III  III  II   II  II  I   illlli  I     m 

tfUinJ        HlH  Illlff  Iff  rill  il  III  HI  HI    ilili  1        1  (If  i                                     1                          1           i !                   i 
1  InHiiil  ill         it  III  1  1  it         1                 1     i      1 1            1               i  HI   u     '    '        1  ' 

11                                                                                                                II 

Hi I      11 H                      Pi 

Bhm 

ftllNUU 

1        i               i                   i 
■  11                    ii 

\m 


lilllll  llll 


111  1 

11 


'Rc^A^ 


r\Vv- 


Itefmnr?  Utbntrg 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/serologyofnervoOOkapl 


SEROLOGY 


OF 


NERVOUS  AND  MENTAL 
DISEASES 


BY 

D.  M.  KAPLAN,  M.  D. 

DIRECTOR   OF   CLINICAL   AND    RESEARCH    LABORATORIES  OF   THE 

NEUROLOGICAL    INSTITUTE,     NEW     YORK    CITY;     SEROLOGIST  TO 

THE   MONTEFIORE    HOME 


ILLUSTRATED 


PHILADELPHIA  AND  LONDON 

W.  B.  SAUNDERS  COMPANY 

1914 


^fo  -  n  0.03 


Copyright,  1014,  by  W.  B.  Saunders  Company 


PRINTED     IN    AMERICA 

PRESS    OF 

W.    B.    SAUNDERS    COMPANY 

PHILADELPHIA 


Dedicated 
to  the  work  of 

The  Neurological  Institute 

New  York  City 


PREFACE 


In  reviewing  the  literature  in  book  form  it  became  appar- 
ent that  there  is  no  American  work  covering  the  subject  of 
serology  in  nervous  and  mental  diseases.  Scattered  articles 
of  merit  are  to  be  found  in  general  and  special  periodicals, 
but  a  collection  of  the  material  in  one  volume  is  sadly 
wanting.  I,  therefore,  thought  that  it  would  meet  with  the 
approval  of  physicians,  particularly  neurologists  and  psychi- 
atrists, to  have  a  volume  in  which  some  of  their  queries  might 
be  answered.  The  chief  stimulus  to  write  such  a  book  came 
from  Dr.  M.  J.  Karpas,  of  the  Psychiatric  Division  at  Belle- 
vue  Hospital,  to  whom  I  wish  to  express  my  sincere  thanks. 
I  am  also  indebted  to  Dr.  H.  Noguchi  for  photographs  and 
suggestions.  The  cooperation  of  the  Medical  Officers  of  the 
Institute  helped  greatly  in  furthering  the  completion  of  this 
work,  and  I  wish  to  close  with  thanks  to  them. 

D.  M.  KAPLAN. 

30  Beekmann  Place, 

New  York  Citt. 

May,  1914. 

11 


CONTENTS 


PART   I— TECHNOLOGY 

Page 

Introduction 17 

History  of  Lumbar  Puncture 17 

Anatomy  and  Physiology 18 

Rachicentesis 19 

General  Considerations  of  the  Spinal  Fluid 24 

Physical  Properties 24 

Chemical  Characteristics 26 

Cytology 32 

Methods  of  Cell  Counting 39 

Interpretation  of  Findings 43 

Serology 47 

The  Various  Modifications  of  the  Wassermann  Reaction ....  73 

The  Controls  and  Their  Significance 75 

The  Performance  of  the  Wassermann  Reaction 77 

PART   II 

The  Serology  op  Nervous  and  Mental  Diseases  of  Non- 

luetic  Etiology 84 

General  Considerations 84 

Meningeal  Affections 85 

Micotic  Meningitis  with  Demonstrable  Bacteria  in  the 

Fluid 85 

Non-micotic  Meningitis 92 

Brain  Diseases 95 

Spinal  Cord  Diseases 100 

Nerve  Affections 109 

Miscellaneous  Affections Ill 

Functional  Nervous  Disorders Ill 

Spasmophilic  States 113 

Vasotrophic  Disorders 115 

Disorders  of  Internal  Secretion 116 

The  Psychoses 117 

Organic  Psychoses 121 

13 


14  CONTENTS 

Page 

Functional  Psychoses 122 

Toxic  Psychoses 123 

Intoxications 128 

PART   III 

The  Serology  of  Nervous  and  Mental  Diseases  op  Luetic 

Origin 132 

Tabes  Dorsalis 132 

Usual  Serologic  Type 134 

Hyperlymphocytic  Type 135 

Negative  Type 136 

Wassermann  Fast  Tabes 138 

Juvenile  Tabes 142 

Monosymptomatic  Tabes 143 

The  Influence  of  Therapy  on  the  Serology  and  Clinical 

Course  of  Tabes 145 

The    Serologic    Interrelationship    Between    Tabes    and 

General  Paresis 149 

Resume 150 

Cerebrospinal  Syphilis 152 

Positive  Spinal  Fluid  Type 155 

Plaut  Type 157 

Acellular  Type 159 

The  Influence  of  Treatment  on  the  Serology  and  Course 

of  the  Disease 160 

The  Transition  of  the  Serology  of  Cerebrospinal  Lues  to 

General  Paresis 165 

Resume 167 

Cerebral  Syphilis 170 

Spinal  Syphilis 172 

General  Paresis 173 

The  Distribution  of  the  Treponema  Pallidum  and  Its 

Detection 174 

The  Theory  of  the  Wassermann  Fast  Phenomenon 176 

The  Serology  of  the  Full-fledged  Type 178 

Other  Serologic  Combinations 179 

The  French  Conception  of  Serologic  Progression 183 

The  Gold  Chlorid  Curve 184 

Gold  Chlorid  Reaction  in  General  Paresis 187 

The  Serologic  Differentiation  Between  Lues  Cerebrospi- 

nalis  and  General  Paresis 190 

Juvenile  Paresis 191 

The  Influence  of  Therapy  on  the  Serology  of  General 

Paresis 193 

Resume  and  Remarks 195 

The  Serology  of  Early  Lues  and  Its  Significance 197 


CONTENTS  15 

PART   IV 

Page 

The  Therapeutic  Use  op  Salvarsan 201 

History  and  Development  of  Salvarsan 201 

Early  Methods  and  Results 210 

Dosage 213 

Injection  of  the  Drug 213 

Preparation  of  Salvarsan 219 

Preparation  of  Patient  for  Injection 222 

The  Technic  of  Injection 223 

111  Effects  Accompanying  the  Injection 227 

After-care  of  the  Patient 228 

Indications  and  Contraindications 229 

The  Water  Error 234 

The  Fate  of  the  Drug  in  the  Organism 235 

The  Detection  of  Arsenic 236 

The  Combined  Intravenous  and  Intraspinous  Treatment 239 

The  Intensive  Intravenous  Method 242 

Post-Salvarsan  Manifestations 247 

The  Amino  (NH2)  Nitrogen  Content  of  Sera 253 

Literature 264 

Index 335 


SEROLOGY  OF  NERVOUS  AND  MENTAL 
DISEASES 


PART   I— TECHNOLOGY 


INTRODUCTION 
HISTORY  OF  LUMBAR  PUNCTURE 

The  credit  for  first  withdrawing  cerebrospinal  fluid  from 
a  patient  ought,  properly,  by  right  of  priority,  to  go  to 
an  American  physician,  Dr.  J.  L.  Corning,  who  performed 
the  puncture  in  1885. l  Essex  Wynter  conceived  the  plan  of 
diminishing  intracranial  pressure  by  performing  ventricular 
puncture.  Later,  in  a  patient  in  whom  the  fontanels  had 
prematurely  closed,  and  it  was  desirable  to  diminish  the 
intracranial  pressure,  the  spinal  route  had  to  be  resorted 
to  for  the  purpose  of  withdrawing  the  cerebrospinal  fluid. 
This  was  performed  in  1889,  and  although  the  technic2  was 
crude,  it  nevertheless  served  as  a  stimulus  to  other  workers 
further  to  elaborate  the  study  of  lumbar  puncture.  The 
first  paper  by  Quincke  on  the  technic  of  lumbar  puncture 
and  the  study  of  the  cerebrospinal  fluid  appeared  in  1891. 
The  thoroughness  with  which  the  subject  was  treated,  and 
the  painstaking  studies  that  followed  on  the  steps  of  the 
German  investigator,  justify  the  coupling  of  his  name  with 
the  operation  of  lumbar  puncture,  in  fact,  with  the  entire 
subject  of  research  work  done  on  the  cerebrospinal  fluid. 
Following  closely  the  publications  of  Quincke  appeared 
those  of  Sicard,  Nissl,  and  others. 

1  "Hand-book  of  the  Med.  Sci.,"  W.  Wood,  vol.  vii,  p.  292. 

2  The  fluid  was  obtained  by  performing  a  laminectomy. 

2  17 


18         SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

ANATOMY  AND  PHYSIOLOGY 

The  spinal  fluid  occupies  the  space  between  the  pia  and 
arachnoid — the  so-called  subarachnoid  space.  It  comes  in 
contact  with  the  periphery  of  the  brain  and  cord,  and  prob- 
ably communicates  with  the  ventricles.  The  subarachnoid 
space  is  traversed  by  very  fine  connective-tissue  trabeculse, 
of  which  but  little  is  known,  although  they  may  assume 
pathologic  importance  when  they  become  thickened  and 
adherent.  Cerebrospinal  fluid  can  be  demonstrated  as 
early  as  the  fourth  month  of  fetal  life,  at  a  time  when  the 
Pacchionian  bodies  are  still  absent.  It  is,  therefore,  unreason- 
able to  suppose  that  these  bodies  have  anything  to  do  with 
the  formation  of  cerebrospinal  fluid.  It  is  more  likely, 
although  this  is  not  definitely  settled,  that  the  fluid  is  a  true 
secretion  of  the  choroid  plexus  cells,  a  theory  advanced 
by  Mott.  Whether  the  fluid  is  to  be  considered  as  a  true 
secretion  or  as  a  transudate  or  as  both,  can  be  ascertained 
from  the  opinions  of  noted  workers  on  this  subject.  It  has 
been  proved  that  the  spinal  fluid  in  patients  with  icterus 
do  not  show  discoloration  in  the  ventricular  fluid,  whereas 
the  spinal  fluid  is  discolored  yellow.  The  increase  in  globu- 
lin, as  found  in  general  paresis,  exhibits  a  similar  peculiarity. 
These  facts  tend  to  show,  among  other  things,  that  a  free 
communication  between  the  ventricles  and  the  subarach- 
noid space  probably  does  not  exist.  The  normal  men- 
inges permit  the  appearance,  in  the  cerebrospinal  fluid,  of 
formalin  after  the  ingestion  of  hexamethylentetramin.  The 
circulation  also  gives  to  the  fluid  its  specific  syphilitic  ambo- 
ceptor. The  appearance  of  blood  in  the  spinal  fluid  after  a 
hemorrhage  in  the  ventricles  cannot  be  considered  as  proof 
that  there  is  a  free  communication  between  the  subarachnoid 
and  the  intraventricular  fluids,  for  it  is  likely  that  the 
trauma  produced  by  the  free  extravasation  of  blood  in  the 
ventricles  would  also  destroy  normal  barriers.  As  against 
this  is  the  fact  that  small  particles  of  sterile  dyes  injected 
into  the  spinal  canal  find  their  way  into  the  ventricles. 
Some  experimenters  have  suggested  an  outlet  for  the  central 
canal  in  the  conus  terminalis  (Kramer). 


RACHICENTESIS  19 

The  chief  function  of  the  cerebrospinal  fluid  is  a  pro- 
tective one,  i.  e.,  the  fluid  serves  as  a  cushion,  preventing 
jarring  of  the  structures  surrounded  by  it.  It  also  tends  to 
neutralize  substances  that  are  to  be  considered  as  excre- 
tory, forming  inert  combinations  of  complex  organic  con- 
stitution. The  presence  of  glucose  in  the  fluid  appears  to 
furnish  an  energy  supply  to  the  nervous  apparatus  (personal 
communication  by  Mott). 

RACHICENTESIS 

Indications. — The  chief  purpose  in  obtaining  cerebro- 
spinal fluid  is  to  secure,  in  doubtful  instances,  an  aid  to 
diagnosis.  It  is  this  feature  alone  that  has  made  spinal  punc- 
ture a  frequent  procedure,  especially  in  neurologic  and 
psychiatric  practice.  The  progress  made  in  the  study  of  the 
fluid  has  furnished  very  practical  and  useful  aids  to  treat- 
ment and  prognosis.  The  not  infrequent  meningeal  mani- 
festations in  children  require  that  a  definite  diagnosis  of  the 
disease  be  made,  which  is  often  impossible  without  the  aid 
of  lumbar  puncture.  It  has  also  been  used  for  therapeutic 
purposes  in  such  conditions  where  the  symptoms  were 
believed  to  be  due  to  increased  intracranial  pressure. 

Contraindications. — First  in  the  list  of  contraindications 
to  lumbar  puncture  must  be  placed  tumors  of  the  posterior 
fossa,  particularly  of  the  cerebellum.  Where  the  necessity 
of  studying  the  fluid  is  very  great  (establishing  a  syphilitic 
disease  of  the  nervous  apparatus),  it  is  permissible  to  with- 
draw at  most  2  c.c.  of  the  fluid,  and  immediately  replace  the 
same  with  an  equal  quantity  of  sterile  normal  saline  solu- 
tion, or  raise  the  foot  of  the  bed  and  keep  the  patient  in  this 
position  for  twenty-four  hours.  It  is  needless  to  warn 
against  puncturing  patients  whose  physical  condition  in 
itself  would  preclude  such  a  procedure. 

Preparation  of  Patient. — It  is  best  to  secure  a  spon- 
taneous bowel  movement  first,  and  if  this  is  not  successful, 
then  a  mild  saline  should  be  given  on  the  morning  of  the 
day  when  the  puncture  is  performed.  In  the  case  of  ambu- 
lant patients,  it  is  advisable  to  do  the  puncture  in  the  even- 
ing, so  that  they  may  rest  overnight.    The  aseptic  precau- 


20        SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

tions  consist  in  the  ordinary  cleansing  of  the  lumbar  and 
upper  sacral  region  with  green  soap,  followed  by  water, 
alcohol,  and  ether.  It  is  not  necessary  to  use  a  stiff  brush, 
an  ordinary  piece  of  sterile  gauze  being  sufficient  for  the 
mechanical  work.  Having  thus  rendered  the  part  aseptic, 
a  piece  of  sterile  gauze  is  placed  across  the  spot  to  be  punc- 
tured, and  secured  by  a  strip  of  adhesive  plaster. 

Technic  of  Lumbar  Puncture. — It  is  best  to  perform  the 
puncture  with  the  patient  sitting  on  a  chair  sideways,  so 
that  the  back  of  the  chair  is  to  one  side  of  the  patient. 
Place  a  pillow  under  the  patient's  abdomen,  pushing  it  well 
back,  and  folding  the  patient's  arms  across  it.  Having 
instructed  the  patient  to  bend  his  spine  into  an  arch  back- 
ward, the  operator  runs  his  index-finger  over  the  spinal 
column  in  an  endeavor  to  locate  the  softest  spot  on  a  level 
with  the  posterior  superior  spines  of  the  ilium.  This  finding 
of  the  most  suitable  point  is  a  matter  of  training,  and  is 
more  reliable  than  measurements  made  with  a  tape  held 
over  the  spines.  When  the  condition  of  the  patient  does 
not  permit  the  use  of  a  chair,  the  puncture  may  be  done 
with  the  patient  in  bed,  lying  on  one  side,  with  his  knees 
well  drawn  up  over  his  abdomen.  The  more  the  back  of 
the  patient  is  bent,  the  greater  will  be  the  distance  between 
the  two  lumbar  spines,  and  the  easier  will  it  be  for  the  opera- 
tor to  find  the  softest  spot.  Having  found  the  spot,  a  slight 
impression  is  made  over  it  with  the  thumb-nail  (previously 
rendered  sterile). 

The  needle  to  be  used  should  be  made  of  flexible  and  not 
of  rigid  material,  as  cases  are  on  record  in  which  the  needle 
broke  and  had  to  be  dissected  out.  The  one  commonly  in 
use  is  about  11  cm.  long  and  of  1  to  1.5  mm.  bore.1  It  is 
provided  with  a  stilet,  which  is  withdrawn  when  the  canal 
is  reached.  In  neurotic  patients  it  is  safest  to  anesthetize 
the  puncture  spot  with  ethyl  chlorid.  The  needle  is  in- 
serted with  a  sudden  thrust,  exactly  in  the  center,  and 
straight  forward.  By  going  to  one  side  and  directing  the 
needle-point  toward  the  patient's  left  one  frequently  en- 

xThe  so-called'  "Quincke  set"  is  an  expensive  apparatus,  and  can 
readily  be  dispensed  with. 


Fig.  1. — Skeletal  relations  of  the  lumbar  puncture.  Note  the  com- 
paratively larger  space  between  the  third  and  fourth  lumbar  spines. 
The  "  soft  spot  "  is  usually  to  be  found  in  this  region. 


Fig.  2. — Posture  of  patient  during  lumbar  puncture.  Note  the 
second  test-tube  in  the  operator's  right  hand.  The  space  between  the 
two  dark  lines  corresponds  with  the  posterior  superior  spines.  The 
needle  is  in  the  space  between  the  third  and  fourth  lumbar  spines. 


RACHICENTESIS  21 

counters  obstacles  that  are  not  met  when  the  median  line 
and  a  straight  thrust  are  used.  It  is  sometimes  desirable  to 
ascertain  the  pressure  of  the  spinal  fluid;  in  such  case  an 
ordinary  3  mm.  tube,  bent  into  a  U,  with  a  small  straight 
limb  provided  with  a  piece  of  rubber  connecting  tubing  is 
employed.  The  long  arm  of  the  U  tube  is  about  90  mm. 
long;  the  short  tube,  30  mm.  Before  using  it  it  should  be 
filled  with  mercury  up  to  30  cm.  A  centimeter  scale  may  be 
attached  to  it,  and  the  rise  of  the  mercury  column  measured 
after  the  cerebrospinal  fluid  begins  to  flow.  Having  ob- 
tained about  6  to  8  c.c.  of  fluid,  the  needle  is  quickly  with- 
drawn, and  the  point  of  puncture  covered  with  a  strip  of 
adhesive  plaster.  It  is  advisable  to  collect  the  cerebrospinal 
fluid  in  two  test-tubes,  in  case  the  first  tube  shows  blood 
contamination.  Occasionally  one  is  unable  to  obtain  spinal 
fluid  even  when  there  is  no  doubt  as  to  the  needle  being 
properly  introduced  into  the  subarachnoid  space;  this  fact 
was  determined  by  W.  M.  Leszynsky,  who,  having  introduced 
a  needle  and  entered  the  canal  in  the  fourth  space  without 
obtaining  spinal  fluid,  demonstrated  the  fact  that  a  dry 
tap  was  the  cause  of  the  non-appearance  by  introducing 
salt  solution  through  a  needle  introduced  in  a  space  higher 
up,  which  appeared  through  the  needle  that  was  left  in  situ 
in  the  previous  puncture. 

Phenomena  Attending  the  Puncture. — It  sometimes  hap- 
pens that,  on  withdrawing  the  stilet,  the  operator  finds  that 
no  fluid  issues  forth;  if  the  patient  is  instructed  to  take  a 
deep  breath,  and  no  result  is  obtained,  one  of  three  things 
is  at  fault:  either  the  needle  has  not  gone  deep  enough  or 
it  has  gone  too  deep  (lodged  in  the  intervertebral  fibrocar- 
tilage),  or  else  it  has  become  clogged  by  a  fibrin  plug  or  by 
some  substance  detached  by  the  needle  during  its  transit  from 
the  skin  to  the  subarachnoid  space.  In  the  first  instance,  and 
provided  the  direction  of  the  needle  is  correct,  a  little  further 
advance  of  the  needle  will  cause  the  fluid  to  flow;  in  the 
second  instance,  withdrawing  the  needle  will  have  the  de- 
sired effect;  when  the  lumen  is  obstructed,  it  is  permissible 
to  reintroduce  the  stilet  and  dislodge  the  occluding  material. 
When  blood  is  obtained  with  the  first  attempt,  it  is  advisable 


22        SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

not  to  attempt  puncture  again,  as  most  likely  the  fluid  is 
contaminated,  and  is  no  better  on  a  second  trial  than  on  the 
first.  It  is  a  peculiarity  of  some  patients  suffering  from 
tabes  or  general  paresis  that  the  introduction  of  the  needle 
is  hardly  appreciated.  It  sometimes  happens  that  the 
needle  strikes  one  of  the  nerve-filaments  in  the  cauda  equina 
bundle ;  this  is  followed  by  a  more  or  less  severe  pain,  affect- 
ing the  area  of  the  nerve  distribution.  There  are  instances 
on  record  where  death  occurred  immediately  after  a  lumbar 
puncture. 

After-care  of  the  Patient. — Some  patients  are  so  little 
affected  by  the  lumbar  puncture  that  it  is  hardly  necessary 
in  these  instances  to  adopt  any  precautions  whatever. 
It  is,  however,  better  and  safer  practice  to  keep  the  patient 
in  bed  at  least  overnight,  where,  if  necessary,  he  can  be 
seen  by  the  doctor.  Other  patients,  again,  suffer  from 
severe  headache  which  may  last  over  a  week.  Lowering  the 
head,  mild  sedatives,  an  ice-bag,  or  any  similar  simple  pro- 
cedure often  suffices  to  overcome  this  after-effect.  If  it  does 
not  abate,  it  is  safe  to  give  in  one  dose  40  gr.  of  sodium 
bromid,  together  with  20  gr.  of  iodid  of  potassium.  If 
necessary  this  may  be  repeated  in  four  hours.  On  the 
other  hand,  patients  of  a  hysteric  temperament  are  likely 
to  suffer  longer  and  more  severely;  such  individuals  may 
vomit  or  develop  a  nervous  diarrhea  and  be  otherwise 
miserable. 

Disposal  of  the  Obtained  Fluid. — A  great  deal  depends 
upon  the  care  the  fluid  receives  after  it  has  been  withdrawn. 
As  the  chief  purpose  of  the  puncture,  in  the  majority  of 
instances,  is  to  aid  in  diagnosis  or  measure  the  progress  of 
treatment,  a  fluid  that  is  placed  in  the  refrigerator  over- 
night or  for  twenty-four  hours  may  at  times  undergo  a 
change  sufficient  to  alter  its  entire  composition.  The  best 
procedure  is  to  count  the  cells  within  an  hour  of  the  with- 
drawal of  the  fluid;  it  seems  that,  when  left  overnight,  some 
fluids  suffer  greatly,  so  far  as  the  cell  count  is  concerned. 
It  is  not  altogether  safe  to  add  a  few  drops  of  formalin  (4  per 
cent.)  to  the  fluid,  as  such  a  procedure  may,  in  some  fluids, 
produce  anticomplementary  properties  and  thwart  the  result 


RACHICENTESIS  23 

of  the  Wassermann  reaction.  For  bacteriologic  purposes, 
the  utensils  employed  should,  it  is  needless  to  say,  be  per- 
fectly sterile.  In  fact,  for  such  work  the  entire  procedure 
must  be  more  carefully  performed:  the  operator's  hands 
must  be  treated  as  for  an  operation;  the  patient's  back 
must  be  thoroughly  cleansed;  the  test-tubes  should  be  sterile 
and  dry,  and  the  fluid  preferably  submitted  at  once  for  bac- 
teriologic analysis.  If  placed  in  the  ice-chest,  and  with  the 
addition  of  a  few  drops  of  a  1 :  3000  tricresol  solution,  cerebro- 
spinal fluid  keeps  fairly  well  for  the  Wassermann  test  for 
three  to  four  days. 


GENERAL  CONSIDERATIONS  OF  THE  SPINAL 
FLUID 

PHYSICAL  PROPERTIES 

Normally,  the  color  of  cerebrospinal  fluid  is  that  of 
clear  water.  At  times  the  admixture  of  red  cells  gives  it  a 
pinkish  hue,  which,  in  view  of  the  traumatic  origin  of  the 
blood,  need  give  rise  to  no  concern.  It  is  in  such  instances 
that  the  advantage  of  using  two  test-tubes  becomes  ap- 
parent. The  fluid  has  a  specific  gravity  that  is  not  constant, 
and  ranges  between  1003  and  1009.  It  is  absolutely  taste- 
less and  odorless. 

In  'pathologic  states  the  color  may  be  unchanged,  and,  in 
fact,  in  the  majority  of  diseased  conditions  of  the  nervous 
system  the  color  is  not  distinguishable  from  that  of  normal 
fluids.  It  is  not  at  all  impossible  for  blood  or  its  products  to 
find  its  way  into  the  subarachnoid  space  after  a  cerebral 
hemorrhage,  provided,  of  course,  that  the  meninges  were 
involved  in  the  bleeding;  experience  teaches,  however,  that 
such  admixtures  are  quite  rare,  and  that  blood  products 
are  more  frequently  the  exception  than  the  rule  in  cerebral 
hemorrhage.  As  will  be  seen  later,  the  change  in  color  is  of 
significance  in  certain  conditions,  and  consequently  it  be- 
comes important  to  be  able  to  differentiate  between  the  true 
color  of  the  fluid  and  that  due  to  the  accidental  admixture  of 
blood  which  is  sometimes  unavoidable;  in  such  instances  the 
color  due  to  cellular  admixture  is  excluded  by  thorough  cen- 
trifugalization.  I  have  observed  that  some  fluids,  besides 
giving  an  intense  protein  excess  reaction,  also  show  a  slight 
yellowish  discoloration,  no  deeper  in  color  than  ordinary 
cedar  oil  (xanthochromia).  Mestrezat  distinguishes  three 
forms  of  xanthochromia,  according  to  its  origin:  (1)  Origine 
serochromique;  (2)  origine  hemolytique;  and  (3)  origine 
icterique.    In  the  majority  of  instances  such  fluids  came  from 

24 


PHYSICAL   PROPERTIES  25 

paraplegic  patients;  I  do  not  wish  to  ascribe  this  peculiarity 
to  tumors  of  the  cord  or  brain,  although  this  abnormity 
was  chiefly  encountered  in  cord  tumors,  but  would  prefer 
to  leave  the  pathologic  significance  of  this  most  interesting 
finding  for  future  observers  to  decide.  At  present  much 
new  matter  is  being  obtained  by  the  safer  operative  pro- 
cedures, showing  us  in  the  living  subject  the  cause  for  such 
deviation  from  the  normal;  I  must  say,  however,  that  where 
the  laboratory  advanced  the  possibility  of  a  tumor  of  the 
cord,  the  clinician  having  made  this  diagnosis  before,  the 
subsequent  operation  did  not  reveal  such  a  condition.  In 
one  instance  there  was  an  endothelioma  with  cysts.  In  a 
few  instances  all  that  was  obtained  was  a  purplish  discolor- 
ation of  the  roots  of  the  cauda  equina. 

Aside  from  the  color,  the  transparency  of  the  fluid  at  times 
suffers  from  pathologic  admixtures.  Instead  of  the  clear 
watery  liquid,  one  sometimes,  although  rarely,  withdraws 
a  turbid,  cloudy  fluid  that,  in  the  majority  of  instances,  is 
due  to  cellular  admixture.  This  is  sometimes  obtained  in 
severe  purulent  affections  of  the  meninges  of  the  brain  or 
cord.  That  pure  pus  may  be  found  is  a  possibility,  though  a 
rare  one. 

The  changes  observed  in  the  pressure  vary  to  such  an 
extent,  even  in  normal  individuals  with  intact  nervous  sys- 
tems, that  it  is  hardly  permissible  to  ascribe  any  great  sig- 
nificance to  its  variations.  Some  tabetics  show  an  increased 
pressure,  whereas  others  do  not;  in  fact,  in  some  it  is  below 
the  normal.  It  is,  however,  important  to  know  to  what  ex- 
tent the  fluid  can  be  withdrawn ;  in  this  instance  the  pressure 
serves  as  an  index.  If  the  pressure  has  fallen  greatly  below 
normal,  in  the  sitting  posture,  and  with  the  use  of  the  water 
manometer, — less  than  100  mm., — then  the  danger  mark  is 
near  at  hand,  and  one  ought  to  be  prepared  to  inject  normal 
sterile  saline  solution  to  replace  the  fluid  withdrawn.  Such 
a  procedure  was  found  necessary  when  a  solution  of  magne- 
sium sulphate  was  injected  into  the  subdural  space  to  over- 
come the  spasticity  of  the  lower  extremities.  The  respira- 
tions in  this  patient  fell  to  8  or  9  a  minute.  Some  interesting 
facts  are  being  elicited  in  the  differences  in  pressure  in 


26        SEROLOGY    OF   NERVOUS   AND   MENTAL   DISEASES 

attacks  of  epilepsy,  but  up  to  the  present  time  (1913)  no 

definite  clinical  benefit  could  be  derived  from  this  knowledge. 

Concerning  the  specific  gravity  of  fluids  in  pathologic 

conditions,  such  as  meningitis  or  hemorrhage,  the  increase, 

if  present,  is  due  entirely  to  the  protein  excess  and  to  the 

number  of  cells,  and  is  proportionate  to  the  increase  of  these 

two  factors. 

CHEMICAL  CHARACTERISTICS 

The  reaction  of  the  normal  spinal  fluid  is  slightly  alkaline, 
and  contains  a  little  over  1  per  cent,  of  solid  matter.  It  is 
capable  of  reducing  Fehling's  solution,  which  reaction,  ac- 
cording to  Mott,  is  due  to  the  presence  of  glucose.  Of  the 
basic  elements,  potassium  is  to  be  found  in  greater  quantity 
than  sodium,  chiefly  in  the  form  of  the  salts  of  phosphorus. 

The  protein  matter  that  is  always  found  in  traces  in  nor- 
mal cerebrospinal  fluids  consists  chiefly  of  globulin  and 
albumose.  Halliburton  demonstrated  the  presence  of 
traces  of  cholin  in  normal  cerebrospinal  fluids.  This  sub- 
stance is  a  product  of  decomposition  of  cerebrospinal  nerve 
matter,  and  is  derived  from  the  breaking  down  of  lecithin 
and  cephalin.  In  some  fluids  traces  of  lactic  acid  may  be 
found. 

Methods  of  Protein  Determination. — Before  considering 
the  occurrence  of  protein  excess,  it  is  essential,  first,  to  con- 
sider the  methods  of  its  detection  and  quantitative  deter- 
mination. This  is  very  important  for  clinical  purposes, 
especially  as  some  methods  give  an  excess,  whereas  others  do 
not.  This  must  be  determined  before  a  conclusion  can  be 
arrived  at  as  to  the  significance  of  an  excess  in  the  work  of 
an  experimenter  who  reports  this  finding.  The  various 
methods  for  the  determination  of  protein  in  the  spinal 
fluid  are  about  the  same  as  those  for  the  finding  of  this  sub- 
stance in  other  media.  These  methods,  however,  had  to 
be  modified  for  cerebrospinal  fluid  work,  and  others  had 
to  be  devised  for  this  purpose.  Aside  from  the  various 
tests  of  complex  nature  which  are  not  suitable  for  the  clin- 
ician, a  few  of  these,  however,  on  account  of  their  simplicity, 
lend  themselves  to  the  needs  of  the  practical  physician.  It 
is  these  tests  that  are,  I  believe,  of  interest  here. 


CHEMICAL   CHARACTERISTICS  27 

The  much  discussed  Phase  1  reaction  consists  of  the  addi- 
tion, to  the  normally  reacting  spinal  fluid,  of  an  equal  quan- 
tity of  neutral  ammonium  sulphate  solution.  This  is  a 
saturated  chemically  pure  ammonium  sulphate  solution 
in  hot  water.  The  Phase  1  reaction  of  Nonne  is  said  to 
be  positive  when,  three  minutes  after  the  addition  of  the 
ammonium  sulphate  solution,  a  turbidity  takes  place. 

In  detail,  the  reaction  of  Nonne  and  Ayelt  is  performed 
as  follows:  2  c.c.  of  cerebrospinal  fluid  are  mixed  with  an 
equal  quantity  of  a  neutral  saturated  solution  of  ammonium 
sulphate  (purissimum,  Merck),  and  compared,  after  three 
minutes,  with  another  tube  containing  spinal  fluid  only; 
if  there  is  no  difference,  or  only  a  very  faint  opalescence,  the 
reaction  is  considered  as  negative.  If  there  is  an  opalescence 
or  a  turbidity,  the  reaction  is  said  to  be  a  positive  Phase  1. 

Zaloziecki,  in  performing  the  Nonne-Apelt  reaction,  uses 
only  0.5  c.c.  of  cerebrospinal  fluid,  carrying  out  the  test  in 
smaller  test-tubes.  I  agree  with  him  in  the  use  of  a  smaller 
amount  of  fluid,  as  it  does  not  in  the  least  alter  the  result 
of  the  test,  and  leaves  the  remaining  fluid  for  other  reactions, 
such  as  the  cell  count,  the  Wassermann  reaction,  the  gold 
solution,  the  Fehling  reaction,  etc. 

A  positive  Phase  1  was  considered  by  Nonne  and  Apelt  as 
significant  of  a  globulin  excess,  and  also  as  evidence  that  the 
fluid  was  obtained  from  a  patient  whose  nervous  system  was 
not  normal.  As  Phase  2  was  considered  the  appearance  of  a 
turbidity  in  normal  fluids  on  the  addition  of  heat  and  acetic 
acid.  Owing  to  the  uncertainty  of  reading  the  end-results 
with  this  method,  its  clinical  application,  so  far  as  a  globulin 
excess  is  concerned,  is  less  popular  than  other  methods  in 
vogue. 

The  Ross-Jones  method  is  a  ring  test,  using  ammonium 
sulphate  as  the  precipitating  reagent.  Carefully  float  1  c.c. 
of  cerebrospinal  fluid  over  2  c.c.  of  concentrated  ammo- 
nium sulphate  solution;  when  a  ring  of  hair-like  fineness  is 
obtained  after  three  minutes,  the  reaction  is  considered  to 
signify  a  globulin  excess.  This  test  is  better  suited  for 
clinical  purposes,  as  the  end  reaction  is  more  constant,  is 
less  influenced  by  individual  interpretation,  and  is  sharper. 


28        SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

Ross  and  Jones  consider  the  importance  of  estimating  the 
thickness  of  the  ring,  the  time  of  its  appearance,  and  the 
performance  of  the  test  with  diluted  fluids. 

The  Noguchi  method,  which  is  very  popular  in  America, 
gives  very  satisfactory  results.  Its  technic  is  as  follows: 
To  0.1  c.c.  of  cerebrospinal  fluid  add  0.5  c.c.  of  a  10  per  cent, 
solution  of  butyric  acid  in  physiologic  salt  solution.  Boil 
this  for  a  short  time,  and  quickly  add  a  quantity  of  a  normal 
solution  of  sodium  hydroxid  equivalent  to  the  amount  of 
cerebrospinal  fluid  used.  After  this  the  mixture  is  boiled 
once  more  for  a  few  seconds.  An  increase  of  protein  matter 
is  characterized  by  the  appearance  of  a  granular  or  flocculent 
precipitate,  which  gradually  settles  to  the  bottom  of  the 
tube.  The  greater  the  excess,  the  more  pronounced  is  the 
precipitate.  If  the  amount  of  protein  matter  is  very  small, 
the  precipitate  does  not  appear  until  after  standing  for  two 
hours.  Such  results  are  not  considered  as  an  excess.  Al- 
though very  well  adapted  to  qualitative  work,  this  method 
does  not  give  a  sufficiently  accurate  gage  regarding  the 
quantitative  relations  of  the  excess. 

Nissl's  qualitative  demonstration  of  globulin  is  made  with 
a  cold  saturated  solution  of  ammonium  sulphate;  his  quanti- 
tative method  entails  the  use  of  a  centrifuge,  after  the  addi- 
tion of  Esbach's  reagent  to  the  spinal  fluid. 

Sippy  and  Moody  used  colloidal  gold,  after  the  Lange 
fashion,  and  reported  results  that  compared  very  favorably 
with  those  obtained  with  the  Nonne  method. 

The  method  of  Lange  is  performed  as  follows:  Four  solu- 
tions are  prepared:  (1)  A  1  per  cent,  gold  chlorid  solution  in 
very  carefully  distilled  water,  using  absolutely  clean  utensils 
throughout;  (2)  a  2  per  cent,  potassium  carbonate  solution; 
(3)  a  1  per  cent,  formaldehyd  solution;  (4)  a  10  per  cent, 
sodium  chlorid  solution.  These  solutions  may  be  kept  in 
stock,  and  are  used  from  time  to  time  to  make  up  the  indi- 
cator. 

Preparation  of  the  Gold  Solution  Indicator. — Into  a 
1000  c.c.  flat-bottom  flask  of  best  Jena  glass  place  500  c.c. 
of  freshly  and  doubly  distilled  water.  The  apparatus  used 
for  the  distillation  should  not  have  rubber  connections  com- 


CHEMICAL   CHARACTERISTICS  29 

ing  in  contact  with  the  steam  nor  with  the  water.  Add  to 
500  c.c.  of  the  water  5  c.c.  of  the  carbonate  solution,  and 
place  on  a  wire  gauze  for  rapid  boiling.  Half  a  minute 
after  the  addition  of  the  carbonate  solution  add  5  c.c.  of 
the  gold  chlorid  solution,  and  permit  the  mixture  to  boil 
up  quickly,  using  two  Bunsens.  As  soon  as  the  first 
bubbles  of  ebulition  appear,  remove  the  flask  from  the 
flame  and  add  gradually  3f  c.c.  of  the  formalin  solution; 
shake  all  the  time  in  a  rotary  fashion  until  the  fluid 
becomes  a  deep  cherry  red.  The  best  way  to  control 
the  color  is  as  follows:  In  an  ordinary  f-inch  test-tube 
place  15  c.c.  of  tV  normal  sodium  hydroxid  solution; 
add  0.2  c.c.  of  a  0.5  per  cent.  Congo  red  solution  and 
0.3  c.c.  of  a  1  per  cent,  alizarin  solution.  The  intensity  and 
the  nuance  of  the  color  in  the  test-tube  as  viewed  by  trans- 
mitted light  correspond  exactly  to  the  depth  and  color  of 
the  indicator  in  the  flask,  viewed  in  a  similar  way.  The 
resulting  solution  should  be  absolutely  clear — so  clear  that 
ordinary  newspaper  print  can  be  read  through  it;  it  should 
not  give  rise  to  the  formation  of  a  bluish  deposit  of  gold  on 
the  sides  of  the  vessel  after  a  few  days'  standing.  Although 
the  solution  keeps  fairly  well,  I  prefer  the  use  of  freshly 
prepared  solutions.  Solutions  with  a  yellowish  shimmer 
should  be  discarded. 

Performance  of  the  Test. — Into  each  of  10  test-tubes  place 
the  salt  solution  made  up  to  0.4  per  cent,  freshly,  from  the 
10  per  cent,  solution.  Each  tube  with  the  exception  of  the 
first  one  receives  1  c.c.  of  the  salt  solution.  Test-tube  No.  1 
receives  1.8  c.c.  of  the  salt  solution.  Into  tube  No.  1  place 
0.2  c.c.  of  the  spinal  fluid  to  be  analyzed.  Mix,  and  remove 
1  c.c.  of  the  fluid.  Place  this  into  tube  No.  2,  and  continue 
the  procedure  until  each  tube  receives  a  gradually  weaker 
dilution  of  spinal  fluid.  Now  add  to  each  tube  5  c.c.  of  the 
gold  solution  indicator  and  mix  well  at  once.  Let  the  fluids 
stand  for  twenty-four  hours  at  room  temperature  and  then 
examine.  A  clear  solution  indicates  a  positive  reaction. 
The  gradation  of  colors  is  from  an  absolutely  colorless  to  a 
red  fluid.     The  first  is  marked  as  5;  the  latter,  as  0. 

Kaplan's  Method.— -In  my  laboratory  the  procedure  used 


30        SEROLOGY   OF   NERVOUS    AND    MENTAL   DISEASES 

is  as  follows:  Into  a  test-tube  1  cm.  wide  and  8  cm. 
long  are  placed  0.5  c.c.  of  the  spinal  fluid  to  be  analyzed. 
It  is  heated  until  it  boils  up  twice;  then  3  drops  of  a  5  per 
cent,  solution  of  butyric  acid  in  physiologic  salt  solution  are 
added,  followed  immediately  by  0.5  c.c.  of  a  supersaturated 
ammonium  sulphate  solution  and  the  fluid  set  aside  for 
twenty  minutes.  In  adding  the  ammonium  sulphate  solu- 
tion care  must  be  taken  to  allow  it  to  flow  under  the  solu- 
tion and  not  to  mix  the  test-tube  contents. 

After  about  twenty  minutes  an  excess  manifests  itself  in 
the  form  of  a  thick,  granular,  pot-cheese-like  ring.  When 
no  granular  thick  ring  forms,  the  fluid  may  be  regarded  as 
normal.  Every  fluid  that  shows  the  ring  just  described  is 
further  tested  as  to  the  intensity  of  the  excess.  For  this 
purpose  four  other  tubes  receive  each  0.1,  0.2,  0.3,  and  0.4  c.c. 
of  spinal  fluid  respectively,  and  each  in  turn  is  brought  up 
to  the  0.5  c.c.  mark  with  distilled  water.  The  same  procedure 
is  followed  as  for  the  first  tube.  The  tubes  are  set  aside  for 
twenty  minutes  and  readings  then  taken.  The  quantity  of 
protein  matter  permitting  a  ring  to  appear  in  the  tube  con- 
taining only  0.1  c.c.  of  spinal  fluid  is  designated  as  0.1  excess, 
and  marks  the  greatest  degree  of  increase.  Fig.  3  shows 
a  0.4  excess.  The  chemical  changes  to  be  observed  in  patho- 
logic fluids  vary  in  different  diseases  and  in  different  forms 
of  the  same  disease.  It  is  to  be  remembered,  at  the  begin- 
ning, that  no  hard-and-fast  laws  exist  for  the  finding  of 
abnormalities  in  pathologic  fluids,  and  that  if  one  ad- 
heres too  closely  to  the  significance  of  laboratory  data 
and  disregards  clinical  findings,  he  will  sooner  or  later  be 
led  into  error. 

Zaloziecki  recommends  highly  the  Pandy  reaction,  which 
he  performs  as  follows:  From  80  to  100  c.c.  of  acidum 
carbolicum  liquefactum  purissimum  are  brought  up  to  1 
liter  with  distilled  water.  The  mixture  is  shaken  thoroughly 
and  placed  in  the  incubator  for  a  few  hours.  After  complete 
clarification  at  room  temperature,  which  requires  several 
days,  the  clear  supernatant  fluid  is  removed  and  used  as  the 
reagent.  It  should  be  kept  at  room  temperature  and  evapora- 
tion avoided,  as  both  tend  to  render  the  reagent  opaque.     A 


Fig.  3. — The  writer's  method  of  estimation  of  a  protein  excess. 
The  above  shows  an  excess  obtained  in  the  tube  containing  four-tenths 
of  a  cubic  centimeter  of  spinal  fluid  and  one-tenth  of  water,  i.  e.,  a 
0.4  excess. 


CHEMICAL  CHARACTERISTICS  '  31 

drop  of  the  fluid  is  permitted  to  trickle  down  the  side  of  a 
watchglassful  of  the  reagent.  The  fluid  must  be  free  from 
blood  and  centrifuged  before  using.  A  mild  reaction  is  char- 
acterized by  the  appearance  of  a  cloudiness  in  the  liquid;  a 
strong  reaction  shows  a  white  precipitate.  The  finer  results 
must  be  viewed  over  a  dark  surface.  This  reaction  is  chiefly 
produced  by  globulins,  but  may  also  be  obtained  with  albu- 
min in  fluids  containing  a  sufficient  salt  content. 

As  was  previously  stated,  the  admixture  of  blood  products 
will  alter  the  color  of  the  fluid ;  besides  this,  such  constituents 
will  also  change  the  qualitative  as  well  as  the  quantitative 
relationship  of  the  chemistry  of  the  fluid.  Hemorrhages 
into  the  nervous  apparatus,  permitting  blood  to  appear  in 
the  fluid,  although  not  giving  it  a  distinctive  discoloration, 
may  be  detected  by  the  different  sensitive  chemical  tests. 
In  using  benzidin,  one  must  be  extremely  careful  not  to 
allow  his  hands  to  come  in  contact  with  the  fluid,  as  per- 
spiration, even  in  traces,  is  capable  of  giving  the  reaction. 
A  yellow  discoloration  of  the  fluid  is  at  times  obtained  in 
icteroid  states.  A  pale,  cedar-oil  color  is  sometimes  obtained 
in  cases  of  spinal  cord  compression.  In  one  instance  it  was 
believed  that  the  color  was  due  to  cystic  fluid,  the  needle 
having  entered  the  cyst.  Upon  operation  it  was  found  that 
an  enormous  endothelioma  encircled  the  cord  for  about  9 
inches,  filling  the  entire  vertebral  canal;  the  tumor  showed 
many  cysts  containing  the  same  colored  fluid  as  the  speci- 
men obtained  by  lumbar  puncture.  It  is  of  interest  to  note 
that  the  fluid  almost  congealed  upon  boiling.  It  is  not  at  all 
improbable  that  the  color  is  a  blood  product,  as  the  fluid  in 
the  case  just  cited  gave  a  Berlin-blue  reaction.  In  uremic 
states  the  quantitative  relationship  of  urea  in  the  fluid  is 
thought  to  be  proportionate  to  the  increase  of  this  substance 
in  the  blood.  As  the  presence  of  cholin  in  the  spinal  fluid  was 
demonstrated  in  normal  states,  and  as  its  quantitative 
determination  involves  considerable  technical  experience, 
this  finding  loses  in  importance  for  the  reasons  just  given. 

In  diabetes  the  sugar  content  may  increase  markedly  in 
the  spinal  fluid.  In  dementia  prsecox  this  constituent  is 
greatly  reduced  in  quantity.    In  two  cases  of  diabetic  coma, 


32        SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

one  in  a  girl  of  sixteen  and  another  in  a  youth  of  seventeen, 
I  was  able  to  obtain  marked  acetone  and  diacetic  acid  reac- 
tions with  the  ordinary  chemical  tests. 

Of  the  drugs  that  enter  the  spinal  fluid  after  their  ad- 
ministration the  foremost  and  the  earliest  studied  is  uro- 
tropin.  In  some  meningitides  iodin  can  be  detected  after 
its  administration.  After  prolonged  narcosis  chloroform  was 
found,  and  some  observers  demonstrated  the  presence  of 
alcohol  in  cases  of  acute  alcoholism.  Wechselmann,  Zalo- 
ziecM,  Sicard,  and  Bloch  were  able  to  demonstrate  arsenic 
in  the  spinal  fluid  after  the  injection  of  salvarsan.  They 
used  the  Marsh  method  and  the  cultural  method  of  Abel. 
(Cultures  of  Penicillium  brevicaule  give  a  distinct  odor  of 
garlic  with  minutest  traces  of  arsenic.)  In  a  search  for 
arsenic  in  patients  similarly  treated  I  was  able  to  demon- 
strate the  presence  of  arsenic  in  a  number  of  spinal  fluids. 
These  tests  were  performed  from  two  days  to  two  weeks 
after  the  last  intravenous  injection  of  salvarsan  and  neo- 
salvarsan.  The  inherent  odor  of  the  bread  culture  of  the 
fungus  is  so  strong  in  itself  that  one  must  possess  the  very 
finest  sense  of  smell  in  order  to  be  able  to  demonstrate  a  faint 
trace;  in  some  instances  an  extraneous  odor  may  give  one 
the  impression  of  garlic. 

The  observation  of  Pappenheim,  that  some  fluids  from 
patients  with  general  paresis  contain  a  leukotoxic  sub- 
stance, is  interesting  from  an  immunity  standpoint. 

CYTOLOGY 

General  Morphologic  Considerations  in  Normal  Fluids. — 
In  the  majority  of  instances  the  small  lymphocyte  is  the  chief 
constituent  of  normal  spinal  fluids.  Here  and  there  one  may 
find  a  cell  with  a  tail-like  prolongation  that,  in  my  opinion, 
has  no  special  significance,  as  it  may  be  found  in  normal  as 
well  as  in  pathologic  fluids.  As  a  result  of  an  unsuccessful 
puncture  the  normal  hematologic  constituents  may  find 
their  way  into  the  spinal  fluid.  This  occurs  at  times  regard- 
less of  the  care  and  the  experience  of  the  operator  who  makes 
the  puncture.  At  times  the  admixture  is  so  slight  that  these 
findings  may  be  disregarded,  and  the  general  morphologic 


CYTOLOGY  33 

picture  may  in  such  instances  be  accepted  as  the  true  ex- 
pression of  the  condition  of  the  cerebrospinal  fluid.  At  other 
times,  when  much  blood  is  accidentally  obtained,  no  definite 
conclusion  can  be  arrived  at  because  of  the  admixture. 

The  normal  quantitative  limits  vary  with  the  worker's 
method.  In  fact,  the  laboratories  using  the  Fuchs-Rosenthal 
chamber  are  at  variance  as  to  the  normal  limits  of  the  cell 
count.  In  view  of  the  meager  knowledge  of  the  normal 
physiologic  limits,  such  as  the  change  in  the  cell  count  after 
a  hot  or  a  cold  bath,  after  massage,  during  gestation,  etc., 
one  is  compelled  to  be  very  conservative  regarding  the  ap- 
proximately true  limit  of  the  cellular  content  in  the  spinal 
fluid.  In  my  experience,  the  maximum  normal  count  can  be 
placed  at  8  per  cubic  millimeter.  Regardless  of  the  care  exer- 
cised by  French  workers  using  the  centrifuge  method,  their 
quantitative  conclusions  are  not  nearly  so  definite  as  are  the 
opinions  of  those  who  use  the  counting  chamber  and  pipet. 

General  Morphologic  Considerations  in  Pathologic  States. 
— That  morphologic  admixtures  may  be  found  in  spinal 
fluids  that  belong  among  the  curiosities  of  medicine  can- 
not be  denied;  in  this  work  only  the  usual  cells  encountered 
in  conditions  that  are  acceptedly  pathologic  will  be  dealt 
with,  and  where  it  is  possible  to  attach  a  clinical  significance 
to  a  given  cell  form,  such  opinion  will  be  expressed.  As 
previously  stated,  the  majority  of  cells  found  in  the  spinal 
fluid  are  small,  poor  in  protoplasm,  and  intensely  baso- 
philic lymphocytes.  The  nuclei  of  these  cells  are  usually 
round,  but  may  at  times  show  a  slightly  oval  contour. 
The  protoplasm  may  seem  to  be  entirely  absent,  and  at 
other  times  may  show  a  slight  accumulation  at  one  pole  of  the 
cell,  or  surround  the  nucleus  with  a  narrow  margin  of  lighter 
staining  cell  protoplasm.  These  small  lymphocytes  are 
smaller,  as  a  rule,  than  the  ordinary  red  blood-corpuscles, 
viewed  with  the  same  power  lens;  those  that  are  larger  and 
show  more  protoplasm  may  be  considered  as  large  lympho- 
cytes. The  differentiation  between  the  small  and  the  large 
has  no  special  clinical  significance,  the  former  being  present 
in  much  greater  quantities  than  the  latter. 

One  frequently  finds,  in  pathologic  fluids,  cells  that  do  not 

3 


34        SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

take  up  the  stain  with  their  usual  avidity  for  bases.  It 
would  seem  that  these  cells  have  lost  the  power  of  ab- 
sorbing the  dye,  and  hence  one  may  consider  them  as  ele- 
ments whose  life  is  on  the  decline,  cells  that  have  served 
their  purpose,  and  do  not  functionate  any  longer.  Such 
cells  may  be  found  even  in  normal  fluids,  and  tend  to  indi- 
cate the  aging  of  the  lymphocyte.  It  is  to  be  observed 
that  when  a  fresh  meningeal  irritation  is  present,  the  small, 
intensely  basic  lymphocytes  predominate;  the  same  fluid, 
obtained  some  weeks  later,  will  show  a  generous  admixture 
of  the  large  forms  plus  the  above-described  poorly  stain- 
able  small  cells. 

It  is  important  for  the  worker  with  but  a  moderate  ex- 
perience to  carry  away  with  him  a  definite  picture  of  these 
poorly  staining  cells,  as  it  is  frequently  difficult  to  differen- 
tiate them  from  the  slightly  degenerated  red  blood-cor- 
puscles that  may  be  present  in  the  same  specimen.  The  old 
lymphocyte  studied  with  the  No.  6  lens  is  no  larger  than 
the  red  cell,  but  upon  focusing  shows  a  definite  flatness;  its 
entire  body  appears  to  be.  covered  with  small  dots,  which 
are  not  granules,  but  protoplasmic  corrugations  the  points 
of  which  lend  the  impression  of  dots.  The  red  cell  is  at 
once  apparent  by  its  gradual  disappearance  upon  focusing, 
showing  differently  refracting  rings  as  the  cell  disappears 
from  view,  the  result  of  its  biconcave  nature.  If  the  red 
cells  are  very  old  (degenerated)  and  have  lost  their  bicon- 
cave form,  they  may,  nevertheless,  be  distinguished  from 
the  old  lymphocytes  by  the  complete  absence  of  the  dotted 
appearance  just  described.  Another  feature  is  the  color: 
the  red  cell  tends  to  assume  a  pinkish  hue,  whereas,  no  matter 
what  the  age  of  the  lymphocyte,  its  former  affinity  for  basic 
dyes  is  still  apparent  in  its  tendency  to  stain  gray. 

An  increase  of  lymphocytes  may  be  observed  whenever 
an  irritation  of  the  meninges  is  present.  The  amount  of 
increase  is  dependent  upon  the  degree  of  the  insult.  It  is, 
therefore,  commonly  observed  in  all  meningitides  and  in  dis- 
eases of  the  meninges  that  are  primarily  or  secondarily  in- 
volved in  luetic  processes,  such  as  tabes,  cerebrospinal  syphilis, 
and  general  paresis.     It  is  reasonable  to  assume  that  in  the 


CYTOLOGY  35 

more  active  manifestations  of  these  diseases  a  greater  variety 
of  cells  and  in  greater  numbers  are  present.  To  attach  diag- 
nostic or  pathognomonic  significance  to  any  special  cell  form, 
with  the  exception  of  specific  tumor  cells,  is  theoretic  and 
not  borne  out  by  proof.  One  variety  of  cells,  however,  the 
plasma  cells  of  Alzheimer,  deserve  special  mention  and  de- 
scription. These  are  large  cells,  with  a  nucleus  that  stains 
very  intensely  with  appropriate  methods,  showing  marked 
chromatin  staining.  The  protoplasm  is  apparently  finely 
granular,  and  shows  a  tendency  to  lighter  staining  in  the 
neighborhood  of  the  nucleus.  The  method  of  obtaining 
this  cell  form,  as  described  by  Alzheimer,  is  as  follows: 
The  cerebrospinal  fluid  is  treated,  preferably  imme- 
diately after  withdrawal,  with  96  per  cent,  alcohol;  about 
3  to  5  c.c.  are  placed  in  a  centrifuge  tube  and  allowed  to 
rotate  for  about  one  hour  at  1000  to  1200  revolutions  a 
minute.  At  the  end  of  this  time  all  protein  matter  will  be 
observed  to  have  collected  at  the  bottom  of  the  tube,  and 
with  it,  of  course,  also  the  cellular  elements.  At  the  end 
of  one  hour  the  96  per  cent,  alcohol  is  replaced  by  absolute 
alcohol,  then  by  ether  alcohol,  and  lastly  by  ether,  at  in- 
tervals of  thirty  to  forty-five  minutes.  The  precipitated 
mass  of  protein  matter  is  disturbed  as  little  as  possible  after 
the  alcohol  centrifugalization,  and  carefully  placed  in  a 
clean  container  with  the  other  media.  The  hardened  sedi- 
ment is  next  placed  first  in  thin  and  then  in  thicker  celloidin, 
and  after  the  latter  is  sufficiently  hardened,  is  ready  for 
cutting.  The  sections  are  made  about  15  micra  thick. 
The  celloidin  is  dissolved  in  methyl-alcohol,  and  the  specimen 
stained  with  the  solution  of  carbol-methyl  green-pyronin  of 
Unna-Pappenheim.  The  staining  should  not  last  longer 
than  a  few  minutes,  and  be  applied  with  gentle  heat,  until 
slight  steaming  is  observed.  The  specimen  is  then  treated 
with  water;  95  per  cent,  alcohol;  absolute  alcohol,  each  for 
a  few  seconds;  next  the  specimen  is  transferred  to  xylol, 
and  lastly  it  is  embedded  in  Canada  balsam.  If  the  fluid 
is  very  poor  in  protein,  it  is  advisable  to  add  a  drop  of  clear 
albumen,  mix  the  fluid  thoroughly,  add  the  alcohol,  and 
centrifuge. 


36        SEROLOGY   OF    NERVOUS   AND    MENTAL    DISEASES 

According  to  the  view  of  Alzheimer  and  those  who  worked 
with  him,  the  finding  of  plasma  cells  in  the  spinal  fluid  is 
highly  suggestive  of  general  paresis.  It  must,  however, 
not  be  forgotten  that  many  cases  of  general  paresis  do  not 
exhibit  these  elements  in  the  fluid;  besides  this,  it  is  not  at 
all  rare  to  find  them  present  in  cerebral  lues.  To  place 
special  significance  because  of  this  on  a  particular  cell  form 
is,  in  my  opinion,  unsafe. 

Many  other  morphologic  forms  are  to  be  found  in  the 
spinal  fluid,  such  as  large  cells  with  eccentrically  placed 
nuclei,  large  cells  (plasma  cells)  with  tails,  cells  with  over- 
lapping nuclei  (neutrophiles?),  etc.  Of  special  interest  in 
this  connection  is  the  leukocyte.  From  a  hematologic 
standpoint,  this  term  covers  the  three  forms  of  granulo- 
cytes— the  eosinophile,  the  neutrophile,  and  the  basophile 
cells.  The  eosinophilic  leukocyte  is  found  but  rarely  in  the 
spinal  fluid,  and  then  only  when  the  fluid  contains  a  large 
number  of  leukocytes,  as  in  a  very  active  acute  meningitis, 
when  the  presence  of  blood,  accidentally  or  pathologically, 
will  sometimes  disclose  an  eosinophile  or  two  in  the  fluid. 
The  basophile  is  rarely  found  in  the  fluid,  and  if  present,  it 
is  usually  the  result  of  the  same  factors  that  are  responsible 
for  the  presence  of  the  eosinophile.  The  neutrophilic  leuko- 
cyte is,  on  the  other  hand,  a  very  common  and  important 
cell  found  in  the  cerebrospinal  fluid.  It  may  be  seen  in  all 
acute  forms  of  meningitis,  such  as  tuberculous,  purulent, 
epidemic  cerebrospinal,  and  in  abscesses  that  invade  the 
subarachnoid  space.  In  acute  forms  of  cerebrospinal  menin- 
gitis luetica  the  presence  of  these  elements  is  an  expression 
of  the  acuity  of  the  inflammatory  process;  they  gradually 
diminish  in  number  as  the  process  tends  to  become  chronic, 
and  in  many  instances  disappear  entirely.  The  so-called 
polymorphonuclear  leukocyte,  as  seen  in  the  counting 
chamber,  shows  one  or  more  nuclei,  which  do  not  take  up 
the  stain  with  the  avidity  characteristic  of  the  lymphocytes 
in  their  young  forms,  but  appear  rather  like  the  old,  worn 
elements  previously  described.  This  phenomenon  is  not  due 
to  age,  but  to  the  fact  that  the  neutrophilic  nuclei  do  not, 
as  a  rule,  take  up  the  basic  stain  as  markedly  as  does  the 


CYTOLOGY  37 

lymphocytic  nucleus.  Besides  these  characteristics,  the 
neutrophilic  cells  are  much  larger  than  the  lymphocytes — 
about  twice  the  size  of  the  red  cells  encountered  in  the 
cerebrospinal  fluid. 

Some  writers  give  elaborate  descriptions  of  the  various 
cellular  elements  to  be  found  in  the  spinal  fluid,  using  the 
schemata  elaborated  by  Pappenheim,  and  describe  neutro- 
philic and  eosinophilic  leukocytes,  microlymphocytes,  micro- 
lymphoidocytes,  lymphoidocytes,  large  monocytes,  endo- 
thelial cells,  plasma  cells,  and  daughter  plasma  cells.  As 
there  is  no  special  benefit  to  be  derived  from  so  elaborate 
a  classification,  and  as  the  search  for  these  elements  con- 
sumes much  time,  I  will  not  enter  into  a  detailed  descrip- 
tion of  this  cytologically  interesting  subject  which  was 
worked  out  by  Szesci. 

Origin  of  the  Cells  in  the  Spinal  Fluid. — The  origin  of  the 
cells  found  in  the  cerebrospinal  fluid  is  by  no  means  a  settled 
point.  Some  workers  claim  that  all  the  cells  found  in  the 
cerebrospinal  fluid  can  be  traced  back  to  the  blood,  and 
others  that  the  cellular  elements  have  a  dual  origin,  some 
being  histogenetic,  others  hematogenetic.  That  the  last  is 
the  best  contention  will  appear  from  the  following  exposition 
of  the  subject:  It  is  to  be  admitted  that,  tinctorially,  most 
of  the  cells  correspond  to  the  elements  to  be  found  in  the 
blood.  The  granulocytes,  with  their  specific  granules,  defi- 
nitely prove  their  relationship  to  the  similarly  stained  cells 
in  the  blood.  On  the  other  hand,  careful  histologic  studies 
of  the  meninges  in  general  paresis  disclose  marked  infiltra- 
tions with  plasma  cells,  which  are  widely  different  from  any 
cells  to  be  found  in  the  blood.  Besides  these  plasma  cells,  one 
often  finds  large  cells  with  various  nuclei,  apparently  collected 
during  their  pojoum  in  the  spinal  fluid.  These  cells  are  ap- 
parently macrophages  of  the  spinal  fluid,  and  serve  as  scav- 
engers. They  originate  in  the  meninges,  and  are  apparently 
sent  into  the  fluid  circulation  in  response  to  a  call  which  is 
always  some  irritation,  be  it  traumatic,  chemical,  or  morpho- 
logic. These  macrophages,  stained  by  the  Alzheimer  method, 
frequently  show  in  their  protoplasm  remnants  of  old  red 
cells,  portions  of  dead  lymphocytes,  and  debris  that  has 


38        SEROLOGY   OF    NERVOUS    AND    MENTAL   DISEASES 

lost  all  distinctive  landmarks.  Pappenheim  is  of  the  opinion 
that  the  cells  in  the  fluid  are  purely  hematogenous,  and  be- 
lieves that  the  fact  that  their  tinctorial  properties  differ 
from  those  in  the  blood  is  to  be  accounted  for  by  the  change 
a  sojourn  in  a  foreign  medium  would  effect.  Szesci,  on  the 
other  hand,  advances  the  opinion  that  the  great  majority  of 
cells  in  the  fluid  are  histogenetic,  and  that  their  origin  may 
be  traced  back  to  a  focus  in  the  meninges  that  show  a  similar 
cellular  infiltration;  in  short,  that  the  pleocytosis  is  an 
expression  of  a  cerebrospinal  peri-arteritis.  Fischer  asserts 
that  the  pleocytosis  obtained  is  only  expressive  of  a  menin- 
geal irritation  somewhere  in  the  neighborhood  of  the  punc- 
ture, and  that  the  greater  the  number  of  cells  obtained,  the 
nearer  to  the  site  of  puncture  is  the  meningitis.  Plaut's 
efforts,  however,  show  that  the  fluid  obtained  at  higher 
levels  corresponds  exactly,  so  far  as  the  number  of  cells  is 
concerned,  with  the  specimens  obtained  from  lower  portions 
of  the  spine.  These  investigations  were  carried  out  with 
the  aid  of  the  counting  chamber. 

In  order  definitely  to  settle  the  dual  origin  of  the  spinal 
fluid  cells  it  is  only  necessary  to  take  into  consideration 
the  large  fibroblastic  elements.  These  cells  are  the  largest 
to  be  found  in  the  fluid;  they  possess  a  large  nucleus,  which 
stains  poorly,  and  may  contain  one  or  two  chromatin  accu- 
mulations that  may  assume  the  appearance  of  nucleoli. 
One  may  at  times  find  a  fibroblast  with  two  nuclei.  The 
most  marked  differentiating  feature  is  the  cell-body;  this 
is  usually  prolonged  into  a  spindle  form  with  fusiform  ex- 
tremities; at  times  a  cell  with  two  tails  is  seen.  That  such 
cells  are  not  to  be  found  in  blood  is  not  to  be  denied.  It 
is  safest  to  assume  that  cells,  such  as  the  lymphocytes  and 
granulocytes,  are  hematogenous  in  origin,  whereas  the  large 
fibroblastic  elements,  the  plasma  cells  and  their  derivatives, 
are  histogenic  in  origin.  We  know  that  all  these  elements 
are  to  be  found  in  the  pia,  and  the  changes  a  cell  may 
undergo  when  once  it  reaches  the  fluid  is  still  an  unsettled 
point  that  will  require  much  investigation  before  a  definite 
conclusion  can  be  arrived  at. 


methods  of  cell  counting  39 

Methods  of  Cell  Counting 

The  French  method  of  counting  cells  in  the  spinal  fluid  will 
receive  only  brief  mention,  as  it  is  now  only  of  historic  in- 
terest. Three  or  4  c.c.  of  the  spinal  fluid  are  placed  in  taper- 
ing centrifuge  tubes  and  permitted  to  centrifuge  at  the  rate 
of  1200  a  minute  for  forty-five  minutes.  The  centrifugaliza- 
tion  over,  the  tubes  are  next  emptied  and  placed  on  filter- 
paper,  upper  side  down,  so  that  as  little  fluid  as  possible  will 
trickle  down  the  sides  of  the  tube.  Without  turning  the 
tube  right  side  up  the  small,  grayish  accumulation  of  thrown- 
down  cells  are  sucked  up  with  a  very  fine  capillary  pipet. 
The  cells  are  next  spread  upon  a  clean,  dry  slide  in  three 
equal  drops.  The  drops  are  dried  in  the  air,  fixed  for  ten 
minutes  in  absolute  alcohol,  and  stained  with  methylene- 
blue  in  the  ordinary  way  for  about  ten  minutes,  washed, 
dried,  mounted,  and  examined.  The  difficulties  of  this 
method  are  manifold:  first,  one  does  not  always  obtain  the 
same  quantity  of  fluid;  this  could,  of  course,  be  overcome 
by  taking  only  2  or  3  c.c.  as  a  standard,  and  vigorously 
shaking  the  fluid  before  pouring  it  into  the  centrifuge  tube. 
The  second  objection  is  the  capillary  pipet,  which  must 
necessarily  be  of  the  same  caliber  (the  life  of  a  fine  capillary 
pipet  at  best  is  not  very  long).  The  drying  in  the  air  is 
another  feature  that  ought  to  be  dispensed  with,  as  such 
treatment  of  the  drop  will  inevitably  distort  the  cells,  making 
the  subsequent  morphologic  analysis  difficult. 

The  Nissl  method,  so  far  as  the  cell  count  is  concerned, 
is  almost  the  same  as  the  French,  and  has  the  same  disad- 
vantages. The  same  idea  has  been  elaborated  by  Fischer, 
Kafka,  and  others,  but,  as  previously  stated,  the  drying, 
the  uneven  sucking  up  of  drops,  and  the  irregularities  of 
the  centrifuge  all  introduce  objectionable  features,  and 
hence  these  methods  are  not  to  be  recommended. 

The  method  of  Alzheimer  is  a  purely  qualitative  one,  and, 
when  used  for  this  purpose  alone,  gives  very  satisfactory 
results.  The  only  correct  method  for  the  estimation  of  the 
number  of  cells  in  the  cerebrospinal  fluid  is  with  the  count- 
ing chamber,  as  described  by  Fuchs-Rosenthal.  The  chamber 
of  Nageotte  is  used  extensively  in  France,  but  permits  of  too 


40        SEROLOGY    OF    NERVOUS    AND   MENTAL   DISEASES 

great  error  in  the  final  result,  besides  requiring  too  much  time 
for  the  estimation  of  cells  in  one  fluid.    The  chamber  of  the 


Fig.  4. — Counting  chamber  of  Nageotte.  The  counting  chamber  is 
to  be  had  in  two  depths,  0.5  or  1.0  mm.  In  counting,  usually  four  long 
spaces  are  computed,  which  gives  the  number  of  cells  in  5  c.mm. ;  this  di- 
vided by  5  gives  the  result  in  1  c.mm.  Either  acetic  acid  or  the  methyl- 
violet  stain  as  used  with  the  Fuchs-Rosenthal  chamber  may  be  em- 
ployed. The  above  calculation  is  to  be  used  with  0.5  mm.  deep  ap- 
paratus. 

French  worker   and   that   of  Fuchs-Rosenthal   are   shown 
in  the  accompanying  diagrams  (Figs.  4  and  5). 

It  is  not  absolutely  essential  for  the  actual  cell  count  to 
employ  the  staining  fluid,  as  the  cells  can  be  easily  dis- 


METHODS    OF    CELL    COUNTING 


41 


cerned  with  the  use  of  ordinary  2  per  cent,  acetic  acid  in- 
stead of  the  dye.  In  my  laboratory  the  methyl-violet  stain 
is  used  not  so  much  as  an  aid  in  counting  the  cells,  as  it  is 
for  the  purpose  of  ascertaining  which  cells  are  fresh,  thereby 
giving  a  clue  to  the  age  of  the  cells  and  the  meningitic  process 
itself;  and,  secondly,  to  determine  the  rapidity  with  which 
they  disappear  after  judicious  treatment.  As  a  rule,  the 
average  cell  in  the  spinal  fluid  is  not  a  representative  of  the 
fully    endowed    functionating    lymphocyte    or    polynuclear 


Fig.  5. — The  Fuchs-Rosenthal  counting  chamber  for  cerebrospinal  fluid. 

cell;  the  elements  found  in  the  fluid  are  more  or  less  devital- 
ized by  a  prolonged  sojourn  in  the  cerebrospinal  fluid  or 
represent  the  normal  expression  of  wear  and  tear,  with  the 
absence  of  certain  characteristics  possessed  by  normal  youth- 
ful elements.  If  a  counting  chamber  with  a  cellular  fluid 
stained  with  the  methy-violet  dye  is  permitted  to  act  on  the 
cells  for  five  minutes  and  then  counted,  it  will  be  observed 
that  the  majority  of  the  cells,  in  a  case  with  a  metaluetic 
nervous  affection,  such  as  tabes,  will  show  that  most  of  the 


42        SEROLOGY    OP    NERVOUS    AND    MENTAL   DISEASES 

cells  are  only  faintly  colored,  and  that  only  here  and  there  are 
elements  to  be  seen  that  exhibit  the  necessary  affinity  for  the 
dye,  which  gives  them  the  blackish-blue  color;  the  remaining 
cells  range  in  depth  of  color  from  a  very  faint  gray  to  a  light 
blue.  In  my  opinion  the  cells  capable  of  taking  up  the  stain 
also  possess  some  of  the  other  qualifications  of  a  cell  that 
is  still  in  a  position  to  exercise  its  functions;  whereas  the 
pale  cell,  I  believe,  is  an  element  incapable  of  function,  and  is 
in  a  stage  preceding  its  complete  dissolution.  With  the  aid 
of  acetic  acid  one  can,  as  a  rule,  determine  the  nuclear  out- 
line of  a  cell  with  much  greater  certainty  than  with  the 
stained  fluid. 

The  Fuchs-Rosenthal  Counting  Method. — The  diagram  of 
the  chamber  shown  in  Fig.  5  is  16  mm.  square  and  0.2  mm. 
deep;  in  these  particulars  it  differs  from  the  ordinary  Thoma- 
Zeiss  blood-counting  chamber,  in  that  the  latter  is  only  1  mm. 
square  and  0.1  mm.  deep.  The  resulting  count  with  the 
blood  chamber  gives  the  number  of  cells  in  fV  mm.  of  blood; 
the  Fuchs-Rosenthal  chamber  gives  the  number  of  cells  in 
-1/  mm.  This  markedly  reduces  the  errors  in  counting,  as 
the  final  result  is  practically  one-third  of  the  entire  number 
of  cells  counted.  In  counting  the  fluid  cells  the  following 
procedure  is  employed :  The  test-tube  containing  the  cerebro- 
spinal fluid  is  vigorously  agitated,  which  distributes  the 
cells  fairly  equally  through  the  medium.  With  an  ordinary 
white  blood-corpuscle  pipet  the  staining  fluid  is  sucked  up 
to  the  mark  0.5,  and  then  vigorously  shaken  again.  After 
permitting  the  cells  to  absorb  some  of  the  stain,  which  re- 
quires about  three  minutes,  a  large  drop  is  placed  on  the 
counting  chamber,  the  cover-slip  is  adjusted,  and  the  speci- 
men is  ready  for  counting.  The  stain  used  for  this  purpose 
is  made  up  as  follows: 

Methyl  violet 0.05 

Glacial  acetic  acid 0.5 

Aq.  dest ad  25.0 

In  order  to  preserve  the  staining  fluid  and  to  prevent 
the  formation  of  fungi  I  am  accustomed  to  add  a  few  drops 
of  a  10  per  cent,  solution  of  phenol.  When,  in  spite  of  this 
precaution,  fungi  and  bacteria  develop,  it  is  best  to  make 


INTERPRETATION    OF    FINDINGS  43 

up  a  new  quantity  of  stain.  This  counting  method  requires 
very  little  fluid,  consumes  but  little  time,  and  can  be  carried 
out  at  the  bedside  of  the  patient.  The  cellular  contour  is  not 
disturbed  in  the  least,  and  the  morphologic  constituents  of 
the  fluid  appear  in  their  unaltered  physiologic  form.  It  is 
to  be  remembered  that  the  fluid  is  to  be  examined  as  soon 
as  possible, — preferably^within  one  hour  after  the  puncture, — 
as  the  cell  content  suffers  through  standing. 

It  is  a  matter  of  training  to  be  able  to  distinguish  the 
various  cellular  types  from  their  appearance  in  the  Fuchs- 
Rosenthal  counting  chamber;  where,  however,  exactitude  in 
determining  the  morphology  of  the  spinal  fluid  is  an  essential 
feature,  it  is  advisable  to  resort  to  the  fixation  and  stain- 
ing methods  previously  mentioned. 

Interpretation  of  Findings 

The  Abnormal  Cell  Count. — The  classification  of  Ravaut, 
who  employed  the  French  method,  does  not  deserve  special 
consideration  on  account  of  the  wide  margin  of  error  inherent 
in  the  counting.  Even  the  improvement  of  Nissl,  who 
counted  the  cells  in  the  entire  specimen  (a  very  tedious  and 
time-consuming  procedure),  does  not  give  as  much  informa- 
tion as  the  counting  chamber  methods.  In  my  experience, 
the  maximum  limit  for  the  normal  cell  count  is  8  lympho- 
cytes per  c.mm. ;  the  border-line  count  from  9  to  15  per  c.mm. ; 
the  pathologic  increase,  15  to  60  cells  per  c.mm.;  hyper- 
lymphocytosis,  60  to  250  per  c.mm.;  acute  meningitic  cell 
count,  from  250  to  2000  per  c.mm. 

These  cell  counts  are  useful  chiefly  for  the  establishment 
of  pathologic  conditions  in  the  meninges;  secondly,  as  an  aid 
to  gaging  the  progress  of  a  given  remedial  agent;  in  fact, 
the  latter  use,  in  my  opinion,  is  the  more  important  one,  and 
the  one  that  gives  greatest  satisfaction  to  the  clinician. 
The  border-line  count,  as  all  such  findings  are,  be  it  a  ques- 
tionable Phase  1  reaction  or  a  weakly  positive  Wasser- 
mann  test,  has  no  particular  significance.  Such  a  result, 
in  the  hands  of  a  physician  who  does  not  know  how  to  weigh 
laboratory  reports,  will  sometimes  be  provocative  of  error 
if  too  much  credence  is  given  such  a  report.    In  order  to  be 


44        SEROLOGY   OF   NERVOUS    AND    MENTAL   DISEASES 

able  to  determine  the  cell  count  in  a  given  spinal  fluid 
satisfactorily  it  is  better  to  perform  another  lumbar  punc- 
ture about  ten  days  later,  and  count  the  cells  again,  in  case 
the  previous  counting  gave  a  border-line  result. 

In  paretic  individuals  who  are  in  their  decline  it  is  cus- 
tomary to  find  border-line  counts;  low  cell  counts  are  some- 
times seen  in  cord  tumors  and  in  cases  of  cerebrospinal 
lues  of  the  endarteritic  form.  The  majority  of  instances 
in  which  the  pathologic  increase  is  obtained  are  in  tabes, 
particularly  in  those  forms  of  the  disease  that  yield  to  spe- 
cific treatment.  To  this  cell  count  can  also  be  added  general 
paresis;  in  fact,  this  disease  is  the  representative  of  the 
small-cell  count  pleocytosis.  Pathologic  increase  in  cells 
(15  to  60)  is  found  in  cases  of  untreated  tabes.  Properly 
treated  cases  of  cerebrospinal  syphilis  of  the  gummatous  and 
the  meningitic  types  exhibit  this  degree  of  increase  in  their 
cell  contents  after  appropriate  therapy.  The  hyperlympho- 
cytic  cell  count  is  found  in  tabes  and  in  the  milder  forms  of 
cerebrospinal  syphilis.  The  purulent  meningitides  show  the 
highest  cell  counts,  and  it  is  in  these  cases  that  it  is  not 
infrequently  impossible  to  count  the  cells  because  of  their 
number.  The  acute  forms  of  cerebrospinal  syphilis  have  also 
their  place  in  this  form  of  cellular  increase;  I  have  observed 
a  case  in  which  the  cells  numbered  1680  per  c.mm.  The 
lowest  of  these  counts  are  at  times,  although  but  rarely, 
found  in  tabes.  The  influence  of  therapy  on  the  cell  count 
in  different  conditions  in  which  a  pleocytosis  exists  will  be 
the  subject  of  a  later  section,  in  which,  also,  the  other  reac- 
tions, such  as  the  Wassermann  test,  the  globulin  excess,  and 
the  Fehling  reduction,  will  also  be  considered. 

A  few  remarks  on  the  bacteriology  of  the  cerebrospinal 
fluid:  In  order  to  secure  an  uncontaminated  specimen  for 
bacteriologic  analysis,  the  fluid  must  be  collected  under 
strict  aseptic  precautions.  Every  utensil  or  instrument  that 
may  come  in  contact  with  the  spinal  fluid  must  previously 
have  been  sterilized.  It  is  also  essential,  once  the  fluid 
begins  to  flow,  to  act  as  quickly  as  possible,  as  undue  ex- 
posure to  the  air  may  contaminate  the  fluid  and  offset  the 
resulting  cultural  work. 


INTERPRETATION    OF   FINDINGS  45 

When  a  bacteriologic  examination  is  required,  it  is  best 
to  make  this  alone,  leaving  other  investigations,  such  as 
blood-pressure  and  collecting  the  fluid  for  chemical  analysis, 
until  a  future  time.  It  is,  however,  advisable  to  note  the 
color  and  the  transparency  of  the  fluid  as  it  flows  into  the 
test-tube,  as  it  is  sometimes  possible  to  exclude  a  purulent 
process  simply  by  observing  the  transparency  of  the  fluid. 
When  a  diagnosis  of  an  acute  cerebrospinal  meningitis  has 
been  made,  it  is  best  to  bring  the  microscope  and  staining 
fluid  to  the  bedside  of  the  patient  and  then  and  there  de- 
termine positively  the  existence  of  such  a  condition.  The 
laboratory  worker  should  bring  with  him  the  necessary  anti- 
meningitic  serum,  place  the  same  in  a  vessel  with  warm 
water,  to  bring  it  to  the  temperature  of  the  body,  and  if  the 
resulting  cell  count  shows  the  existence  of  a  meningitis, 
regardless  of  the  bacteriology,  which  is  as  yet  undetermined, 
the  serum  should  be  injected  at  once,  as  the  delay  necessi- 
tated by  the  growing  of  the  bacteria  may  permit  the  disease 
to  progress  beyond  hope  of  repair.  On  the  other  hand,  if 
the  microscopic  analysis  shows  an  absolutely  normal  spinal 
fluid,  one  may  wait  to  ascertain  the  result  of  bacteriologic 
analysis,  and  for  the  time  being  treat  the  patient  symptomat- 
ically.  If  this  method  were  resorted  to  more  often,  fewer 
spontaneous  cures  of  epidemic  cerebrospinal  meningitis 
would  have  been  reported. 

The  search  for  tubercle  bacilli  is  performed  as  follows: 
The  spinal  fluid  is  placed  into  a  centrifuge  tube,  and  three  or 
four  absorbent  cotton  threads  are  added ;  this  is  permitted  to 
centrifuge  for  one  hour,  at  the  end  of  which  time  the  col- 
lected mass  on  the  bottom  of  the  tube  is  poured  into  a  Petri 
dish  over  a  black  surface,  and  the  material  enmeshed  in 
the  cotton  threads  is  carefully  extracted  and  placed  on  a 
glass  slide.  The  fluid  is  gently  evaporated,  and  stained  by 
the  Ziehl-Neelson  carbolfuchsin  method.  At  best,  the 
search  for  tubercle  bacilli,  even  if  they  are  present,  is  a  very 
time-consuming  process,  and  should  not  be  given  up  before 
the  entire  slide  has  been  thoroughly  examined.  This  may 
require  an  hour  or  two;  if  the  fluid  submitted  for  examina- 
tion does  not  show  a  pleocytosis,  half  an  hour  is  sufficient 


46        SEROLOGY   OF   NERVOUS   AND    MENTAL   DISEASES 

for  the  microscopic  work.  The  more  painstaking  procedure 
is  suggested  for  fluids  in  which  a  pleocytosis  was  found. 
Of  the  microbic  invaders  of  the  spinal  canal,  the  most  diffi- 
cult to  detect  is  the  tubercle  bacillus.  The  other  bacilli 
and  cocci  lend  themselves  much  better  for  microscopic 
determination.  Of  these,  the  pneumococcus  shows  itself 
to  greatest  advantage;  the  Micrococcus  intracellularis  can 
also  be  readily  detected;  the  influenza  bacillus  and  the 
ordinary  pus-cocci  show  definite  microscopic  pictures. 
Although  the  microscopy  of  a  fluid  and  the  finding  of  the 
invader  are  frequently  sufficient  for  clinical  purposes,  one 
should  not  depend  upon  the  result  of  such  an  analysis,  espe- 
cially when  the  exact  biology  of  the  microorganism  is  of  in- 
terest. For  accurate  bacteriologic  work,  special  methods 
are  necessary,  requiring  the  assistance  of  a  trained  bacte- 
riologist. The  fluid  is  best  collected,  under  the  precaution 
previously  outlined,  in  a  Petri  dish,  adding  the  nutrient 
medium,  blood-agar,  glucose-agar,  or  plain  agar,  and  sub- 
mitting the  specimen  to  the  specialist  for  further  elabora- 
tion. In  order  to  be  certain  that  the  proper  technic  and 
subsequent  disposal  of  the  collected  fluid  are  properly  carried 
out  it  is  best  to  leave  the  entire  procedure  to  the  bacteri- 
ologist. 


SEROLOGY 

History  and  Development  of  the  Wassermann  Reaction. — 

The  work  of  Bordet  and  Gengou,  who  in  1901  described 
the  method  of  detecting  antigens  and  introduced  it  into 
practice  for  many  diseases,  needs  but  to  be  mentioned  here. 
By  the  term  "antigen"  is  understood  any  substance  capable 
of  producing,  in  a  susceptible  living  organism,  a  definite  and 
specific  response;  this  response  is  the  formation  of  anti- 
bodies. The  nature  of  the  latter  substances  is  still  an 
unsettled  question,  but  it  is  fairly  well  established  that  anti- 
bodies belong  to  the  class  of  amboceptors.  The  entire  reac- 
tion depends  upon  the  mixing  of  a  given  antigen  with  its 
homologous,  inactive  (heated  at  56°  C.)  immune  serum  and 
complement.  In  case  the  immune  serum  is  of  homologous 
nature  with  the  antigen,  the  complement  is  bound  or  devi- 
ated; at  least  it  is  rendered  ineffective  for  further  use.  This 
is  established  by  the  method  introduced  by  Bordet  and 
Gengou,  who  added  a  well-washed  (serum-free)  suspension 
of  erythrocytes,  together  with  a  definite  quantity  of  a  spe- 
cific hemolytic  serum,  which  was  also  heated  to  56°  C.  If 
the  previously  introduced  complement  is  deviated  or  bound, 
no  hemolysis  will  ensue,  as  no  complement  remains  to  com- 
plete the  hemolytic  reaction.  When  the  complement  is  not 
deviated,  hemolysis  takes  place  and  serves  as  a  proof  that  the 
serum  added  to  the  antigen  was  not  of  a  homologous  nature. 
This  method,  therefore,  serves  as  an  indicator  as  to  the  ex- 
istence of  an  amboceptor  that  may  fit  a  given  known  anti- 
gen. Taking,  as  an  example,  a  serum  from  a  case  in  which 
typhoid  is  suspected,  the  following  procedure  would  be  used : 
The  suspected  serum  is  rendered  inactive  (heated  for  one 
hour  at  56°  C.)  and  placed  in  a  test-tube;  to  this  is  added 
our  known  antigen  (Bacillus  typhosus);  next  a  given  quan- 
tity of  complement  is  added  (guinea-pig  serum).  In  order 
to  give  this  combination  an  opportunity  to  unite,  the  mix- 

47 


48        SEROLOGY   OF    NERVOUS    AND    MENTAL    DISEASES 

ture  is  placed  in  an  incubator  for  one  hour.  If  the  serum 
is  that  of  a  typhoid  patient  (contains  the  homologous  im- 
mune body),  we  expect  a  deviation  of  complement.  After 
an  hour's  incubation  the  erythrocytes,  plus  their  hemolytic 
amboceptor,  are  added  to  the  same  mixture  and  the  test- 
tube  is  again  placed  in  the  incubator.  If  the  complement 
is  free,  a  proof  that  the  serum  originally  subjected  to 
the  test  did  not  contain  the  homologous  antibody,  hemo- 
lysis will  take  place  in  from  fifteen  to  fifty  minutes.  If, 
on  the  other  hand,  the  patient  had  typhoid,  hemolysis,  for 
obvious  reasons,  will  not  ensue.  Pictured  diagrammatically, 
the  following  scheme  is  helpful : 


.Typhoid  bacillus 
.Typhoid  amboceptor 
.Complement 


(~\  ....Erythrocytes 


N 


....Hemolytic 
Amboceptor 


Figs.  6, 


This  diagram  shows  theoretically  the  existing  conditions 
when  the  patient's  serum  contains  the  immune  amboceptor 
necessary  for  the  binding  of  the  complement.  If  the  patient 
is  not  suffering  from  typhoid,  and  consequently  does  not 
possess  the  amboceptor,  the  following  diagrams  will  tend 
to  illustrate  what  happens : 


w 


Typhoid  bacillus 

...Any  amboceptor  (except- 
ing typhoid) 


(~)  ....Erythrocytes 


....Hemolytic 
Amboceptor 


....Complement 


Figs.  8,  9. 

Hemolysis  is  the  result  of  this  combination,  and  is  proof 
that  the  patient  does  not  suffer  from  typhoid  fever,  as  the 


SEROLOGY  49 

complement  was  left  free  to  act  on  the  subsequently  intro- 
duced hemolytic  system. 

The  next  step  in  elucidating  the  foregoing  phenomenon 
of  complement  deviation  in  typhoid  was  the  study  of  similar 
deviations  with  various  antigens.  Wassermann,  Neisser, 
and  Bruck  established  the  fact  that  apes  treated  with  re- 
peated injections  of  organic  extracts  from  syphilitics  showed, 
in  their  sera,  substances  that  were  capable  of  binding  com- 
plement with  organic  extracts  (antigen?)  of  syphilitic  origin. 
Next,  Detre,  Wassermann,  Neisser,  and  Bruck,  as  also 
Schucht,  found  that  the  same  holds  true  with  sera  ob- 
tained from  patients  who  were  infected  with  syphilis.  The 
early  results  were  not  very  encouraging,  as  only  a  small  per- 
centage of  cases  gave  this  reaction.  Citron,  however,  proved 
that  the  reaction  is  rarely  obtained  in  recently  infected  in- 
dividuals, as  well  as  in  old,  symptom-free  luetic  patients. 
A  similar  absence  of  phenomenon  was  observed  by  him  in 
well-treated  syphilitics.  This  author,  on  the  basis  of  the 
results  obtained  in  Krauss's  clinic,  advised  the  performance 
of  the  test  as  a  routine  procedure  in  all  cases  where  syphilis 
was  suspected.  The  elaboration  of  the  theoretic  part  of 
the  reaction  is  due  largely  to  the  labors  of  Porges  and  Meier, 
Landsteiner,  Mueller,  and  Poetzl,  and  later  to  Levaditi  and 
Yamanouchi.  These  workers  obtained,  with  the  use  of  alco- 
holic extracts  from  syphilitic  livers  and  other  organs,  very 
satisfactory  substitutes  for  the  still  but  little  known  syphilitic 
antigen.  The  contention  at  that  time  was  that  the  entire 
phenomenon  is  an  interaction  of  various  more  or  less  complex 
lipoids.  Porges  and  Meier  believed  that  the  lipoid  bodies 
were  closely  related  to  lecithin.  Levaditi  and  Yamanouchi 
again  ascribed  the  antigenic  role  of  their  organic  extracts  to 
bile  salts.  The  experiments  of  Wassermann  and  Citron 
showed  that,  at  least  so  far  as  animal  experimentations 
show,  there  is  no  evidence  that  antigenic  qualities  can  be 
ascribed  to  lecithin  or  allied  substances. 

These  workers  also  proved  that  deviation  of  complement 
can  be  obtained  with  such  substances  as  glycogen,  albu- 
mose,  pepton,  lecithin,  oil,  gelatin,  etc.,  a  finding  that  was 
corroborated  by  the  experiments  of  Landsteiner  and  Stan- 

4 


50        SEROLOGY    OF   NERVOUS    AND   MENTAL   DISEASES 

kovic.  These  results  make  it  probable  that  the  phenomenon 
of  complement  deviation  is  due  to  a  change  in  the  physico- 
chemical  relationship  of  a  molecule  through  the  addition 
of  another  substance,  a  view  also  shared  by  Bordet  and  Gay 
in  their  conception  of  hemolysis. 

If  this  is  really  so,  then  the  interesting  work  of  Seligmann 
finds  an  explanation — i.  e.,  that  the  reaction  is  a  physico- 
chemical  change  of  a  colloid  molecule  when  another  sub- 
stance ("Reagin,"  Citron)  is  introduced.  This  last  inves- 
tigator obtained  complement  deviation  with  a  colloid  iron 
hydroxid  solution,  with  emulsions  of  mastic,  with  gelatin, 
etc.  For  the  purposes  of  immunodiagnosis  it  suffices  to 
know  that  whatever  the  colloid-like  antigen  may  be,  it  is 
specifically  influenced  by  homologous  immune  sera,  and 
hence  is  very  useful  for  the  detection  of  unknown  antibodies 
(Reagines). 

At  present  the  application  of  the  phenomenon  of  comple- 
ment deviation  as  a  serodiagnostic  method  for  the  detec- 
tion of  syphilis  receives  more  attention  than  for  any  other 
infectious  disease,  especially  since  the  work  of  Citron  estab- 
lished its  significance  for  lues  in  general;  Wassermann  and 
Plaut,  as  well  as  Marie  and  Levaditi,  for  the  presence  of 
complement  deviating  substances  in  the  cerebrospinal  fluids 
of  general  paretics. 

Technic  of  Blood-taking. — This  procedure,  in  the  hands  of 
an  expert,  is  accomplished  in  not  more  than  one  or  two 
minutes  from  the  beginning  of  sterilization  to  the  finished 
bandaged,  punctured  arm.  One  who  has  no  experience, 
however,  will  frequently  lose  much  time  and,  in  the  end, 
have  secured  no  blood  for  analysis,  and,  besides,  the  patient 
will  have  a  bruised  and  aching  arm.  For  these  reasons  it  has 
been  deemed  well  to  describe  the  technic  fully,  and  show  how 
an  apparently  difficult  puncture  can  be  easily  and  success- 
fully made.  Special  apparatus  are  unnecessary,  and  the 
method  does  not  require  a  special  procedure;  the  essential 
points  to  know  are  how  to  handle  a  vein  and  to  become 
acquainted  with  the  peculiarities  of  veins  in  general.  The 
area  of  the  puncture  is  first  inspected ;  in  my  practice  I  prefer 
to  use  the  left  arm,  for  the  simple  reason  that  the  vein  selected 


SEROLOGY  51 

runs  in  the  line  of  the  needle  puncture,  i.  e.,  from  right  to 
left  and  upward,  which  is  exactly  the  direction  of  the  thrust 
of  the  needle's  point  in  right-handed  operators.  The  in- 
spection should  take  in  the  general  contour  of  the  arm,  and 
especially  the  bend  of  the  elbow.  The  bend  is  carefully  pal- 
pated, in  case  there  are  no  visible  veins,  and  if  none  are  to 
be  felt  upon  palpation,  it  is  advisable  to  exert  a  slight  pres- 
sure two  to  three  inches  above  the  bend.  Sometimes  the 
veins  are  so  deeply  situated  that  a  tourniquet  must  be  ap- 
plied before  the  vein  can  be  felt.  For  educational  purposes 
I  advise  that  one  finger  be  trained  for  the  palpation  of  veins; 
this  advice  may  seem  superfluous,  but  I  have  found  that 
where  others  could  not  find  a  vein,  the  well-trained  finger 
detected  the  slight  resistance  and  the  puncture  gave  blood 
at  the  first  attempt.  It  is  commendable  to  devote  five  min- 
utes to  getting  the  bearings  on  the  venous  distribution  be- 
fore attempting  to  puncture  an  arm.  Most  every  one  has 
witnessed  the  repeated  puncturing  of  an  arm  until  it  re- 
sembles a  sieve.  One  is  to  be  particularly  warned  against 
trying  to  puncture  a  thin-walled,  superficially  lying  vein 
that  is  not  sufficiently  fixed  by  perivenous  connective  tissue. 
The  secret  of  success  lies  largely  in  the  ability  to  select  a 
proper  vein  to  puncture.  This  is  not  always  the  largest 
one,  but,  on  the  contrary,  the  firm,  thick,  small,  and  well- 
fixed  vein,  which  nine  times  out  of  ten  will  receive  the  needle- 
point without  swerving  and  slipping  from  under;  of  course,  if 
properly  manipulated.  The  proper  method  of  manipulating 
an  arm  for  puncture  can  be  divided  into — (a)  the  selection 
of  the  vein;  (6)  rendering  the  vein  prominent  and  harder; 
(c)  fixation  of  the  vein;  (d)  handling  of  the  needle. 

(a)  As  previously  stated,  the  most  sensitive  finger  is  em- 
ployed for  palpation  of  the  bend  of  the  elbow.  These  sug- 
gestions, of  course,  apply  to  cases  in  which  difficulty  is  ex- 
perienced in  finding  veins  for  puncture.  With  slight  inter- 
mittent pressure  the  finger  palpates  the  deeper  soft  parts 
of  the  elbow;  if  a  string-like  resistance  is  obtained  and  the 
sense  of  touch  is  not  delicate  enough  to  distinguish  a  vein 
from  a  tendon,  then  a  tourniquet  is  applied  and  the  area  again 
palpated.    With  the  finger  still  on  the  suspected  vein,  the 


52        SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

tourniquet  is  suddenly  released:  if  the  finger  is  on  a  vein, 
then  the  swelling  or  the  resistance  will  suddenly  collapse;  if 
it  is  on  a  tendon,  the  resistance  will  remain  unaltered.  Should 
no  satisfactory  vein  be  obtainable  on  the  left  side,  then  the 
right  side  should  be  tried;  under  no  circumstances  should 
the  needle  be  plunged  into  a  spot  before  ascertaining  whether 
it  is  a  proper  vein  or,  perhaps,  no  vein  at  all. 

(6)  Having  found  what  appears  to  be  a  vein,  the  next 
step  is  to  make  it  fit  for  puncture.  The  area  is  rubbed 
gently  with  95  per  cent,  alcohol,  and  the  tourniquet  is  ap- 
plied, as  previously  stated.  In  using  a  tourniquet,  a  simple 
piece  of  good  rubber  tubing  is  preferable  to  the  instruments 
sold  in  the  shops  for  the  purpose.  The  tubing  is  of  the 
caliber  of  a  good-sized  catheter,  and  18  inches  long.  The 
pressure  must  not  be  too  great,  as  in  that  case  the  artery  may 
be  obliterated;  it  is,  therefore,  advisable  for  beginners  to  feel 
the  pulse  before  proceeding  further.  With  the  tourniquet  in 
position,  the  next  step  is  to  bring  out  the  vein  as  prominently 
as  possible.  This  is  accomplished  by  dropping  from  a 
bottle,  a  drop  at  a  time,  95  per  cent,  alcohol  on  the  spot  to 
be  punctured,  gently  rubbing  the  trained  finger  over  the 
spot.  When  enough  resistance  to  the  finger  is  experienced, 
then  the  vein  is  ready  to  be  punctured. 

(c)  All  precautions  can  be  frustrated  if  the  vein  to  be 
punctured  is  not  properly  fixed  by  the  operator's  left  hand. 
Care  must  be  observed  to  prevent  the  vein  from  slipping 
from  under  the  needle-point,  as  it  often  will.  For  this  reason 
a  firm  hold  on  the  vein  should  be  obtained  before  the  punc- 
ture is  made.  Figs.  10  and  11  illustrate  graphically  the  points 
to  be  observed  in  this  connection,  and  also  demonstrate  the 
reason  why  the  left  arm  is  more  suitable  than  the  right. 
With  the  thumb  of  the  left  hand  over  the  vein,  firm  pressure 
is  exerted  on  it,  the  entire  attention  being  directed  toward 
this  spot,  the  object  being  to  prevent  slipping  of  the  vein 
from  under  the  thumb  as  well  as  to  guide  the  needle-point. 
If  the  needle  is  in  the  vein  lumen  and  has  pierced  all  the 
coats  of  the  vein-wall,  the  hand  holding  the  needle  will 
experience  a  sudden  sense  of  diminished  resistance,  which, 
in  the  majority  of  instances,  is  followed  by  the  trickling  of 


1 

<U 

0)  T3 

0 

■+3 

"!bJD 

= 

> 

S-i 

C   CD 

2 

+= 

~r 

B 

T3 
03 

0) 

o 

CD 

d 

— 

g 

0.M 

a 

+= 

'53 
> 

— 
03 

o 

DC 

.2  ^ 

03 

<3 

£H 

CD 

+= 

a, 

O 

<3 

■§oo?J° 


a  5 


f^^' 


■    c  —    - 
^_  a; 

CD  .3 

>  += 
^  <d  ,-. 

9  s'«> 

2  -^  ^ 

"H   d   O 


aS  cS 


Fig.  12. — The  author's  equipment  for  taking  blood  for  the  Wasser- 
mann  reaction,  consisting  of  a  rubber  tourniquet  16  inches  long  and  a 
test-tube  outfit  as  seen  on  the  left  of  the  photograph,  which  shows  the 
gauze  bandage  and  the  strip  of  adhesive.  Inside  of  the  tube  is  the 
needle,  the  hilt  of  which  is  inside  of  a  rubber  tube  one  inch  long.  The 
individual  parts  are  shown  to  the  right  of  the  photograph. 


SEROLOGY  53 

blood  from  the  free  end  of  the  needle.  It  is  to  be  rioted  that 
in  patients  with  tabes  the  blood  flows  very  slowly,  regard- 
less of  the  large  but  flabby  vein.  The  instrument  used 
in  obtaining  blood  for  the  Wassermann  test  is  very  simple, 
and  can  be  carried  with  ease  in  one's  vest-pocket.  As  shown 
in  Fig.  12,  it  consists  of  an  ordinary  test-tube  into  which  is 
placed  a  19  gage  needle  If  inches  long.  Around  the  test-tube 
is  placed  a  piece  of  zinc  oxid  adhesive  plaster  half  an  inch 
wide  and  about  four  inches  long.  To  this  adhesive  strip 
is  attached  a  small  gauze  pad  consisting  of  eight  layers  of 
gauze,  about  three-quarters  of  an  inch  wide  and  about  1^ 
inches  long.  The  adhesive  and  the  gauze  serve  the  purpose 
of  a  dressing  after  the  blood  has  been  withdrawn.  The 
entire  outfit  is  sterile.  For  safety  it  is  best  to  carry  the  test- 
tube  in  a  wooden  or  paste-board  container,  especially  after 
the  blood  has  been  collected.  The  free  end  of  the  needle  is 
provided  with  a  piece  of  rubber  tubing  about  one  inch  long, 
which  is  held  in  the  test-tube  while  the  blood  is  being  with- 
drawn.   Test-tube  and  needle  can  all  be  held  with  one  hand. 

(d)  It  sometimes  happens  that  the  needle,  turned  with 
the  slant  down,  as  in  Fig.  10,  will  slip  for  this  very  reason, 
and,  so  to  speak,  glide  along  on  the  outside  of  the  vein. 
The  angle  of  the  needle  at  times  is  faulty,  and  it  will  not 
penetrate.  Therefore  the  direction  of  the  needle's  point  is 
not  to  be  at  too  great  an  angle,  nor  is  the  point  to  be  too 
far  from  the  fixing  thumb.  Having  forced  the  needle  through 
skin  and  vein-wall  in  one  thrust  and  with  a  quick  movement, 
the  direction  of  the  needle  is  slightly  deflected  downward 
and  pushed  further  into  the  lumen  of  the  vein  for  about  3 
or  4  millimeters.  Sometimes  five  to  ten  seconds  elapse 
before  the  blood  begins  to  flow,  as  said  before,  a  condition 
frequently  observed  in  tabes. 

In  collecting  the  blood  for  a  Wassermann  test  I  usually 
hold  the  test-tube  and  needle  as  in  the  accompanying  illus- 
tration (Fig.  11).  Sometimes  one  is  sure  that  he  is  in  the 
vein,  but,  nevertheless,  the  blood  does  not  flow.  This  may 
be  due  to  one  of  the  following  reasons:  The  needle  may 
have  gone  through  the  other  side  of  the  vein-wall;  in  this 
case  very  gentle  withdrawal  for  about  1  or  2  millimeters  will 


54        SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

establish  the  blood-flow;  the  slant  of  the  needle  rests  against 
the  anterior  vein-wall:  in  this  case  a  slight  bending  of  the 
needle  upward  without  going  deeper  will  be  sufficient  to 
cause  the  blood  to  appear.  It  sometimes  happens  that  the 
needle  passes  between  the  layers  of  the  vein-wall:  a  slight, 
gentle  push  will  overcome  this.  For  purposes  of  analysis 
about  6  to  7  c.c.  of  blood  are  sufficient.  It  should  be  em- 
phasized here  that  during  the  manipulation  of  the  vein  the 
patient  should  make  a  fist  and  direct  his  attention  away 
from  the  arm  to  be  punctured.  It  is  best  to  have  the  arm 
bandaged  before  permitting  the  patient  to  look  around 
again.  Before  the  collected  blood  is  placed  in  the  ice-chest 
it  should  be  permitted  to  remain  at  room  temperature 
for  a  few  hours.  This  procedure  will  frequently  obviate 
the  necessity  for  centrifuging  the  blood  to  obtain  the  clear 
serum,  a  time-saving  expedient  not  to  be  lost  sight  of  where 
many  tests  are  to  be  made.  If  the  methods  described  for 
bringing  into  prominence  a  deeply  situated  vein  prove 
futile,  as  is  very  often  the  case  with  babies  and  with  patients 
with  very  stout  arms  and  small,  undeveloped  veins,  the 
following  procedures  are  recommended:  A  bit  of  can- 
tharides  plaster,  one  inch  square,  is  placed  on  the  pectoral 
region  of  a  baby,  and  left  there  for  three  hours.  To  pre- 
vent scratching  and  undue  pressure  a  padding  of  absorbent 
cotton  should  be  placed  about  the  plaster.  It  is  highly  im- 
portant that  the  formed  blister  is  obtained  intact  during 
the  removal  of  the  dressing.  With  a  sterile  hypodermic 
syringe  aspirate  the  formed  serum,  being  at  the  same  time 
prepared  to  catch  into  a  test-tube  any  serum  that  may  escape 
through  the  puncture  made  by  the  needle.  Another  and  a 
more  rapid  way  is  to  sterilize  the  area  between  the  shoulder- 
blades,  and,  with  an  absolutely  sterile  scarifier,  make  a  quick 
incision  and  aspirate  the  blood  with  a  small  Bier  cup.  This 
method  is  also  applicable  to  children  with  inaccessible 
veins,  as  well  as  to  adults  and  dementia  prsecox  patients,  who 
frequently  prove  very  rebellious  and  make  the  ordinary  ways 
of  obtaining  blood  for  the  Wassermann  reaction  impossible. 
Instrumentarium. — The  chief  and  most  frequently  used 
instrument  in  performing  the  Wassermann  reaction  is  the 


SEROLOGY  55 

pipet.  For  ordinary  work,  several  dozen  of  1  c.c.  pipets 
graduated  into  yu  and  into  y^  are  required.  These  should 
be  graduated  to  the  tip  (as  should  all  pipets  for  the  test), 
and  the  distance  from  the  tip  to  the  mark  0  should  not  be 
less  than  13  inches;  this  gives  to  each  iV  c.c.  a  distance  of  1.3 
inches.  The  error  with  smaller  pipets  is  too  great,  and 
they  should,  therefore,  not  be  used.  The  10  c.c.  pipets  are 
those  of  the  ordinary  Mohr  pattern,  graduated  into  j  and 
into  halves.  For  ordinary  work  one  dozen  of  these  suffice. 
Several  gross  of  5  by  -f  test-tubes,  of  good  glass,  not  too 
thin  walled;  a  few  50  and  100  c.c.  graduated  cylinders;  one 
dozen  100  and  250  c.c.  glass  beakers  with  griffin-lip;  half  a 
dozen  each  of  250  and  500  c.c.  Erlenmeyer  flasks;  a  dozen 
wooden  double  row  (6  in  a  row)  test-tube  racks  to  fit  the 
test-tubes;  a  few  large  Petri  dishes;  ordinary  needles  for 
obtaining  the  blood;  these  are  1|  inches  long,  and  have 
a  No.  19  bore  (for  children  it  is-  advisable  to  have  a  No.  20 
bore  needle).  The  free  end  of  these  needles  is  provided  with 
a  small  piece,  of  rubber  about  one  inch  long,  which  lies  in 
the  lumen  of  the  test-tube  when  the  blood  is  being  with- 
drawn. Where  no  vein  can  be  obtained,  as  in  very  young 
infants,  a  wet-cup  is  made  use  of  and  the  blood  sucked 
up  with  a  sterile  Bier  cup.  An  incubator  and  a  thermostat 
of  good  copper,  double  walled,  the  former  to  have  two  com- 
partments, each  provided  with  reliable  thermoregulators. 
The  latter  is  an  important  feature,  and  for  this  reason  I 
recommend  the  Lautenschlager  pattern.  One  razor;  one 
Luer  syringe,  of  10  c.c.  capacity  one  animal  cage  for  rabbits 
and  one  for  guinea-pigs;  one  centrifuge,  capable  of  making 
at  least  1500  revolutions  a  minute  (the  centrifuge  is  to  be 
protected  by  a  brass  bowl,  and  should  be  provided  with  a 
rheostat);  one  dozen  centrifuge  tubes;  one  dozen  ordinary 
drinking-glasses,  with  cotton  on  the  bottom;  a  few  blue  pen- 
cils for  writing  on  glass;  one  shaking  apparatus.  A  half  dozen 
each  of  1  liter  and  \  liter  glass-stoppered  bottles;  one  ice- 
chest.  (For  the  inactivation  of  the  patient's  sera  and  for 
the  storing  of  the  amboceptor  small,  thin-walled  test-tubes 
should  be  used;  for  an  average  laboratory  one  gross  of  these 
suffice.)     A  blow-pipe  outfit  with  good  bellows;  one  dozen 


56        SEROLOGY    OF   NERVOUS    AND   MENTAL   DISEASES 

Bunsen  burners.  Of  chemicals  and  reagents,  the  following 
will  be  found  useful:  Squibb's  sodium  chlorid;  alcohol,  95 
per  cent.;  acetone,  ether,  tricresol,  phenol,  collodion,  freshly 
distilled  water.  It  is  my  opinion  that  a  known  syphilitic 
and  a  known  non-syphilitic  serum  should  be  regarded  as 
the  biologic  reagents  in  a  laboratory  equipped  for  making 
the  Wassermann  reaction.  Laboratories  far  removed  from 
abattoirs  will  have  to  keep  their  own  sheep,  a  few  rabbits, 
and  a  dozen  or  more  guinea-pigs  (the  latter  should  be  full 
grown). 

Rationale  of  the  Test  and  Its  Specificity. — This  was  con- 
sidered at  length  under  the  caption  of  History  and  Develop- 
ment of  the  Wassermann  Reaction.  It  is  based,  as  the  pre- 
vious exposition  tends  to  show,  upon  a  using  up  of  comple- 
ment and  the  detection  of  this  phenomenon.  Primarily  it 
is  an  antibody-detecting  biologic  test.  It  is  believed  that  the 
extract  from  organs  containing  spirochetes  are  as  useful 
for  the  making  of  a  specific  antigen  as  the  antigen  of  typhoid 
bacilli  is  for  detecting  typhoid.  As  no  methods  for  the 
proper  cultivation  of  the  spirochetes  of  syphilis  existed  in 
1906,  making  this  method  of  preparing  antigen  impossible, 
the  technic  advanced  by  Wassermann  and  his  collaborators 
was  employed.  It  soon  became  apparent  in  America  and 
abroad  that  the  views  held  regarding  the  specificity  of  the 
reaction,  and,  in  fact,  the  entire  principle  involved,  had  to 
be  modified.  Much  and  Eichelberg,  who  worked  with 
watery  luetic  extracts,  reported  a  positive  Wassermann  reac- 
tion in  50  per  cent,  of  their  scarlatina  cases.  These  ob- 
servers stated  that  although  the  reaction  was  not  so  vivid 
as  the  florid  lues  reaction,  it  was,  nevertheless,  positive. 
Weichselmann  and  Meier  obtained  positive  reactions  with 
the  sera  from  lepra  patients  by  using  as  antigens  the  watery 
extracts  of  luetic  livers,  alcoholic  extracts  of  normal  organs, 
and  lecithin.  A  later,  more  extensive  study  showed  that  the 
majority  of  the  florid  tuberous  leprosy  cases  gave  a  positive 
reaction  with  syphilitic  extracts  as  well  as  with  tuberculin. 
These  authors  reported  that  the  maculo-anesthetic  form 
of  this  disease  was  incapable  of  complement  deviation.  The 
same  results  were  obtained  by  Slatineanu  and  Danielopolu. 


SEROLOGY  57 

Levaditi  found  a  positive  result  in  the  cerebrospinal  fluid 
from  a  patient  with  sleeping  sickness.  In  7  cases  of  sclero- 
derma the  writer  was  able  to  obtain  a  positive  reaction  in  6. 
These  were  cases  of  the  advanced  form  of  the  disease,  and 
showed  an  involvement  of  the  face,  hands,  and  knees. 
Morphea  gives  a  negative  result.  I  also  called  the  attention 
of  my  co-workers  to  the  fact  that  sera  having  the  color  of 
old  Canada  balsam  (jaundiced?)  will  at  times  give  a  posi- 
tive Wassermann  reaction,  and  cautioned  against  assuming, 
as  a  result  of  the  test,  that  the  patient  had  syphilis. 

These  observations  and  many  others  detracted  greatly 
from  the  specificity  of  the  test,  and  made  conservatism  of  in- 
terpretation an  extremely  important  constituent  of  the 
laboratory  worker's  equipment.  This  conservatism  is  not 
only  to  be  urged  in  regard  to  the  entire  significance  of  the 
test,  so  far  as  its  specificity  for  syphilis  is  concerned,  but 
should  also  govern  every  step  of  the  performance  of  the 
test.  The  laboratory  worker  should  never  attempt  to  de- 
fend his  position  when  the  result  he  obtains  does  not  coincide 
with  the  clinician's  diagnosis;  for  the  clinician  is  probably 
right,  having  a  score  or  more  reasons  for  his  opinion,  whereas 
the  laboratory  worker  relies  only  on  his  reagents,  and  these 
have  peculiarities  still  unknown  to  immunology.  This  will 
be  discussed  further  in  the  section  dealing  with  the  attitude 
of  the  serologist.  It  may  be  stated  here  that  the  larger  the 
experience  of  the  serologist,  the  greater  the  specificity  of  the 
reports  from  his  laboratory,  and  vice  versa. 

Technic  of  Preparation  of  the  Various  Reagents. — The 
reagents  used  in  the  test  are  the  complement,  the  ambo- 
ceptor, the  antigen,  and  the  sheep's  blood-corpuscles.  What- 
ever the  reagent  used,  no  distilled  water  must  be  allowed 
to  come  in  contact  with  it,  else  its  presence  may  produce  a 
hemolytic  effect.  Only  salt  solutions  should  be  employed 
throughout  the  test.  Squibb's  NaCl  (C.  P.),  0.9  per  cent., 
in  fresh  distilled  water,  is  the  solution  used  in  the  writer's 
laboratory.  The  first  reagent  to  be  considered  is  the  com- 
plement. 

Concerning  the  Complement. — For  this  purpose  full-grown 
guinea-pigs  are  preferable  to  younger  animals,  since  their 


58        SEROLOGY    OF    NERVOUS    AND    MENTAL  DISEASES 

complemental  powers  are  more  stable,  and  sufficient  serum 
is  obtained  from  one  animal  to  make  about  40  tests.  The 
smaller  guinea-pigs  will  rarely  give  more  than  2  to  4  c.c.  of 
serum.  The  animal  is  held  over  a  large  Petri  dish,  and  bled 
to  death  by  severing  the  carotid  artery  with  a  good  razor. 
This  is  practically  painless,  the  procedure  lasting  about  a 
second.  At  most  the  pigs  do  not  suffer  greatly,  and  are 
practically  dead  in  a  minute  or  two.  In  severing  the  carotid 
care  must  be  taken  not  to  injure  the  esophagus,  as  this  may 
cause  an  admixture  of  gastric  juice  with  the  blood  and 
minimize  its  ultimate  value.  It  is  important,  in  holding  the 
guinea-pig,  to  keep  the  hindquarters  well  away  from  the 
Petri  dish,  as  it  sometimes  happens  that  the  animal  will  pass 
urine  during  the  exsanguination  and  make  the  comple- 
mental power  less  uniform  and  efficient.  The  blood  is  col- 
lected in  a  sterile  dish,  covered  with  another  larger  vessel, 
and  kept  at  room  temperature  overnight.  I  usually  kill  an 
animal  the  night  before  the  test  is  to  be  made,  and  pipet  off 
the  clear  serum  the  first  thing  in  the  morning.  It  seems  to 
me  that  the  complement  left  thus  overnight  gains  strength 
and  is  more  efficient  than  the  guinea-pig  serum  used  on  the 
same  day  as  the  killing.  Gay  and  Ayer  determined  the  fact 
that  sera  left  together  with  the  coagulum  for  twenty-four 
hours  gain  in  complemental  powers. 

Concerning  the  place  of  origin  of  the  complement,  I  be- 
lieve that  the  theory  advanced  by  Metchnikoff  cannot  be 
maintained.  This  author  believes  that  the  complement  is 
entirely  dependent  upon  the  breaking  down  of  leukocytes. 
Experiments  by  Semnittzky,  however,  showed  that  leuko- 
penic bloods  do  not  contain  less  complement  because  of  it. 
Further  researches  by  Donath  and  Landsteiner  showed  that, 
on  the  contrary,  exudates  rich  in  leukocytes  possess  anti- 
hemolytic  qualities.  The  chief  argument  against  Metchni- 
koff's  theory  is  furnished  by  Hoke,  who  found  that  leuko- 
cytes are  capable  of  binding  complement,  and  that  when  a 
serum  (complement)  is  brought  in  contact  with  leukocytes, 
its  complemental  power  is  thereby  diminished.  Neefeld  is 
of  the  opinion  that  leukocytes  do  not  secrete,  give  off  during 
coagulation,  nor  contain  complement  at  any  time.     The 


Fig.  13. — Holding  guinea-pig  for  obtaining  complement. 


SEROLOGY  59 

many  studies  that  helped  to  overthrow  one  view  did  not, 
however,  supply  another  one  instead,  and  it  is  still  an  open 
question  today  where  the  complement  comes  from. 

It  seems  to  me  that  the  existence  of  many  complements 
(Ehrlich  and  Morgenroth)  renders  the  finding  of  its,  or  rather 
their,  origin  a  very  difficult  task,  and  one  that  will  require 
much  study.  The  function  of  the  complement  in  the  Was- 
sermann  reaction  is  to  complete  the  work  of  the  amboceptor, 
whatever  its  function  may  be.  Without  its  help  the  hemo- 
lytic amboceptor,  for  example,  cannot  lake  the  red  cell,  al- 
though it  is  anchored  to  it.  In  the  Wassermann  reaction  the 
amboceptor-antigen  combination,  if  they  fit  one  another, 
and  only  then,  attract  and  take  up  the  complement  in 
the  test-tube.  No  complement  absorption  takes  place  if  the 
amboceptor  is  foreign  to  the  antigen,  and  is  still  available 
for  work  when  an  opportunity  is  offered,  such  as  by  the 
subsequent  addition  of  an  amboceptor  and  an  antigen  that 
are  homologous,  i.  e.,  fit  each  other. 

The  Preparation  and  the  Properties  of  the  Hemolytic 
Amboceptor. — The  hemolytic  amboceptor  is  the  only  true 
antibody  that  one  deals  with  in  the  Wassermann  reaction. 
It  is  the  reagent  used  in  the  second  stage  of  the  Wassermann 
test,  namely,  the  hemolytic  incubation.  This  phase  of  the 
reaction  can  justly  be  called  the  most  important  part  of  the 
test,  as  those  who  are  unfamiliar  with  the  work  will  commit 
errors  more  frequently  here  than  at  any  other  time  during 
the  test;  this  is  because  at  this  stage  judgment  is  the  chief 
prerequisite  of  the  worker. 

Whether  one  uses  the  antisheep  or  the  antihuman  sys- 
tem, the  animal  used  to  produce  this  amboceptor  is  always 
the  rabbit.  The  making  of  a  good  amboceptor  is  very  im- 
portant, and  not  always  a  success.  One  finds  rabbits  that, 
for  some  reason,  will  not  react  in  the  production  of  an  am- 
boceptor of  sufficient  strength. 

It  is  preferable  to  immunize  male  rabbits  of  about  5  pounds' 
weight.  The  process  of  immunization  is  as  follows:  The 
blood  from  a  freshly  killed  sheep  is  defibrinated  in  a  sterile 
vessel.  The  fluid  blood  is  centrifuged  at  least  five  times, 
and  washed  each  time  with  0.9  per  cent.  NaCl  solution. 


60        SEROLOGY   OF    NERVOUS    AND   MENTAL   DISEASES 

The  sheep-cells  are  poured  into  a  10  c.c.  all  glass  syringe 
(sterile),  and  the  rabbit's  ear  is  prepared  for  the  injection. 
The  ear  is  washed  with  soap  and  water,  shaved,  washed  with 
alcohol  and  ether,  and  the  thumb  of  the  assistant  is  placed 
at  the  root  of  the  ear  to  impede  the  venous  flow  and  thereby 
bring  the  vein  out  to  its  full  extent.  The  needle  of  the 
syringe  should  not  be  very  long,  and  of  about  20  gage. 
Having  dilated  the  vein  as  much  as  possible,  the  point  of  the 
needle  is  forced  gently  into  the  ear  vein,  preferably  into  the 
apex  of  the  inverted  V,  and  a  slight  up-and-down  move- 
ment made  to  ascertain  if  the  needle  is  in  the  lumen.  In 
case  it  is  not,  the  forward  movement  will  be  obstructed; 
besides  this,  a  vein  that  is  punctured  will  show  a  hematoma 
as  soon  as  the  piston  of  the  syringe  injects  a  drop  or  two  of 
blood.  It  is  useless  to  attempt  to  inject  blood  into  a  vein 
thus  injured,  as  it  will  invariably  collect  on  the  outside, 
and  result  in  a  badly  sloughing  ear.  Only  when  the  needle 
can  be  freely  moved  and  the  few  drops  of  blood  do  not  pro- 
duce a  swelling  should  the  blood  remaining  in  the  syringe  be 
emptied  into  the  vein. 

The  proper  manipulation  of  the  rabbit's  ear  requires  a 
little  practice,  but  more  frequently  furnishes  a  good  ambo- 
ceptor than  the  peritoneal  method  of  immunization.  I 
am  accustomed  to  inject,  the  first  time,  about  3  c.c.  of  blood, 
to  which  are  added  2  c.c.  of  NaCl  solution.  The  second  in- 
jection, of  5  c.c.  of  cells  and  3  c.c.  of  NaCl  solution,  is  given 
five  days  later,  also  intravenously,  and  the  animal  carefully 
observed.  From  now  on  the  average  rabbit  begins  to 
elaborate  the  required  amboceptor  and  should  receive  all 
the  care  possible,  including  good  food,  such  as  fresh  cabbage 
leaves,  carrots,  and  oats,  and  fresh  air  and  exercise.  I  know 
of  instances  in  which  six  rabbits  had  to  be  sacrificed  before 
a  proper  amboceptor  could  be  obtained,  hence  the  advisabil- 
ity of  adopting  the  prescribed  care  suggested  above.  In  the 
majority  of  cases  the  full  value  amboceptor  can  be  had  in 
from  eight  to  ten  days.  On  the  eighth  day  after  the  second 
injection  a  little  blood  is  obtained  from  the  ear  vein  by  a 
quick  cut  with  a  keen  razor;  this  is  centrifuged  for  about 
fifteen  minutes,  and  the  clear,  supernatant  serum  collected  for 


Fig.  14. — Intravenous  injection  of  blood  for  obtaining  the  ambo- 
ceptor. Note  that  during  the  injection  no  lateral  swelling  of  the  vein 
takes  place,  a  sign  that  all  of  the  blood  is  properly  injected. 


SEROLOGY  61 

a  preliminary  gaging.  If  the  serum  shows  a  hemolytic  power 
capable  of  laking  1  c.c.  of  a  5  per  cent,  suspension  of  cells  in 
a  dilution  of  1 :  1500  or  1 :  2000  in  about  thirty  minutes,  then 
the  rabbit  is  ready  for  bleeding.  This  is  best  done  on  the 
following  day,  i.  e.,  nine  days  after  the  last  injection.  If 
the  hemolytic  power  is  not  strong  enough,  then  one  ought 
to  wait  a  day  or  two  more  and  then  test  again.  It  is  some- 
times necessary  to  repeat  the  injection  a  third  time  and 
wait  again,  but  it  has  been  my  experience  that  such  rabbits 
do  not  furnish  a  good  amboceptor,  even  if  injected  again 
and  again.  In  such  instances  anti-amboceptor  production 
must  be  thought  of.  Assuming  that  the  hemolytic  power  of 
the  rabbit's  blood  is  great  enough,  the  animal  is  exsanguinated 
the  next  day,  and  the  blood  caught  in  a  sterile  large  glass 
bowl  and  kept  covered  for  twelve  to  sixteen  hours.  The 
expressed  serum  is  now  ready  for  storing  in  the  ice-chest. 
As  will  be  noted,  I  do  not  use  the  method  of  heating  at 
56°  C.  I  believe  that,  since  the  complement  is  easily  de- 
stroyed by  age,  and  since  the  dilution  of  the  rabbit's  serum  is 
so  great,  it  is  not  necessary  to  diminish  the  hemolytic  powers 
of  the  amboceptor  by  a  temperature  of  56°  C.  My  ambo- 
ceptor was  not  capable  of  hemolyzing  a  5  per  cent,  sus- 
pension of  cells  in  an  eight  times  concentration  without 
the  addition  of  complement.  This,  in  my  estimation,  is 
sufficient  proof  that  the  trace  of  complement  present  either 
becomes  inert  after  a  short  time,  or  is  not  sufficient,  in  its 
complemental  powers,  to  complete  the  laking  of  the  cells. 
I  do  not,  therefore,  inactivate  my  amboceptor.  I  believe 
that  good  amboceptors  are  often  rendered  useless  by  this 
preliminary  inactivation — an  observation  that,  I  am  sure, 
others  will  corroborate. 

After  the  complete  separation  of  the  hemolytic  immune 
serum  it  is  placed  in  small  sterile  test-tubes, — 2  c.c.  in  each, 
to  which  is  added  a  tricresol  solution  1 :  2000, — and  the  tops 
are  sealed  with  the  blow-pipe,  permitting  enough  space  so  as 
not  to  heat  the  top  of  the  serum.  This  is  best  accomplished 
by  holding  the  tube  between  fingers  level  with  the  serum 
in  it.  Such  a  hemolytic  amboceptor  is  serviceable  for  three 
to  four  months.    Of  course,  it  is  not  capable  of  hemolyzing 


62        SEROLOGY    OF    NERVOUS   AND    MENTAL   DISEASES 

cells  in  the  same  titer  as  at  the  original  standardization,  but 
if  this  original  titer  was  about  1 :  2000,  then  such  an  ambo- 
ceptor can  be  used  until  none  remains.  A  good-sized  rabbit 
should  yield  from  50  to  70  c.c.  of  amboceptor. 

The  preliminary  standardization  of  the  amboceptor, — i.  e., 
the  gaging  before  the  animal  is  exsanguinated — is  performed 
as  follows: 

PRELIMINARY   STANDARDIZATION   OF  THE  A.   S.   A.1 


Comple- 
ment. 


Sheep  Cells 

5  Per  Cent. 

in  NaCl. 


A.  S.  A.     ,    XaCl  0.9 
1  C.c.       Pee  Cent. 


Result  Afteb  Incubation  at 
37°  C. 


0.1  c.c. 


1  c.c. 


1:200 

1:400 

1:800 

1:1600 

1:3200 


Up  to  5  c.c. 


Hemolysis  usually  in  5  minutes. 

6 

15 

40 

75 


The  rabbit's  serum  that  furnishes  an  A.  S.  A.  of  the 
above  potentiality  is  admirably  suited  for  complement 
deviation.  There  are  many  instances  in  which  it  becomes 
necessary  to  employ  very  strong  amboceptors,  and  unless 
one  has  a  powerful  hemolytic  serum  to  begin  with  such  an 
increase  is  often  impossible.  The  amboceptor  as  standard- 
ized above  is  in  actual  use  in  my  laboratory,  and  hemo- 
lyzes  in  a  still  greater  dilution  in  one  hundred  and  five 
minutes  (1:6400).  For  the  actual  performance  of  the 
Wassermann  reaction  the  foregoing  standardization  will 
not  suffice.  It  is  necessary  to  take  into  consideration  every 
ingredient  of  the  test-tube  that  makes  up  the  complete 
reaction,  as  I  was  able  to  show  repeatedly.2  Where  the 
above  gaging  only  is  made  use  of,  a  goodly  number  of  posi- 
tive reactions  will  be  obtained  from  innocent  persons.  In 
order  to  avoid  this  I  intend  to  gage  my  reagents  in  such  a 
manner  as  to  exclude,  so  far  as  possible,  such  interpretations; 
in  fact,  I  would  prefer  to  report  many  luetic  sera  as  negative, 
for  the  sake  of  eliminating  positive  reactions  in  those  who 
did  not  come  in  contact  with  this  infection.  As  the  normal 
patient's  serum  and  the  antigen  used  are  in  themselves  in- 

1  Anti-sheep  amboceptor. 

2  Kaplan,  New  York  Med.  Jour.,  September  7,  1912. 


Fig.  15. — Instruments  used  in  obtaining  and  gaging  the  amboceptor. 
The  two  long  white  lines  in  the  foreground  of  the  illustration  are  vari- 
ous pipets  for  measuring  small  quantities  of  serum. 


SEROLOGY 


63 


hibitory  factors,  it  is,  therefore,  necessary,  in  the  standardiza- 
tion of  the  amboceptor,  to  take  cognizance  of  these  factors, 
and  gage  the  amboceptor  accordingly.  The  amboceptor  pre- 
viously standardized,  gaged  with  the  antigen  and  a  normal 
serum,  gave  the  following  titer: 

STANDARDIZATION   OF   A.   S.   A.,   TOGETHER   WITH   THE 
ANTIGEN   AND   NORMAL  SERUM 


Normal 
Serum. 

Anti- 
gen. 

Comple- 
ment. 

Sheep 
Cells. 

A.  S.  A. 
1  C.c. 
Sol. 

Hemolysis. 

0.2  c.c. 

JU. 

0.1  c.c. 

©    3     . 

OHM 

a 

1  c.c. 

1 
1 
1 
1 
1 
1 

200 

400 

800 

1600 

3200 

6400 

43    lH 

(3  O     . 

"~.3 

o  CO  ja 
CI 

Complete  in     7  minutes. 

"     11 

"     36 

"  102 

"  150 
Incomplete. 

The  standardization  together  with  antigen  and  serum 
shows  us  that,  not  only  is  hemolysis  slower  in  appearance, 
but  also  that  the  1 :  6400  dilution  did  not  hemolyze  com- 
pletely. It  is  also  apparent  that  the  1 :  3200  dilution  required 
two  and  a  half  hours  for  complete  hemolysis;  this  is  too  long 
a  period  for  actual  work,  and  consequently  cannot  be  con- 
sidered in  establishing  the  working  unit.  Since  the  principle 
underlying  the  establishment  of  the  working  unit  requires 
that  the  dose  should  be  twice  the  size  of  the  dilution  that 
hemolyzed  the  given  quantity  of  cells  in  two  hours,  it  be- 
comes apparent  that  the  A.  S.  A.  unit  for  work  is  somewhere 
between  1 :  800  to  1 :  1000.  Since  the  first  titration  would 
have  given  us  an  A.  S.  A.  of  much  weaker  power,  and  the 
chances  of  error  with  its  actual  use  would  also  have  been 
much  greater,  it  is  quite  evident  that  the  method  of  pre- 
liminary standardization  is  not  applicable  to  actual  work. 
Regardless  of  the  care  and  apparent  overdosage  of  the  A.  S.  A., 
it  has  happened  occasionally  that  the  entire  array  of  tests 
showed  marked  resistance  to  hemolysis.  Although  the 
standardization  on  the  day  of  the  tests  gave  a  working  unit 
of  1:600,  the  hemolysis  was,  nevertheless,  very  sluggish, 
and  required  a  great  deal  of  care  to  distinguish  the  true 
from  the  masked  negatives.  This  occurred  often  enough 
to  demand  investigation.     In  my  laboratory  this  phenom- 


64        SEROLOGY    OF  NERVOUS   AND    MENTAL   DISEASES 

enon  was  designated  as  the  low-power  amboceptor,  and 
would  manifest  itself  on  days  showing  more  than  the 
average  barometric  changes;  on  such  days  persons  with 
rheumatic  tendencies  usually  complain  of  joint  or  mus- 
cular tenderness.  It  was  very  interesting  to  note  that 
the  amboceptor  unit  changes  considerably  on  such  days, 
as  the  table  below  will  show. 

The  Loiv-power  Amboceptor. — The  amboceptor  used  for 
this  titration  gave,  on  a  day  with  the  barometer  at  755  and 
the  temperature  at  22°  C,  a  maximum  hemolytic  power  of 
1:3200  in  ninety-eight  minutes.  A  few  days  later,  with 
the  barometer  at  763  and  the  room  temperature  at  21°  C, 
the  following  values  were  obtained: 


Normal 
Serum. 

Anti- 
gen. 

Comple- 
ment. 

Sheep 
Cells. 

A.  S.  A. 

Hemolysis. 

0.2c.c. 

|U. 

CUcj.c. 

O  d 

a 

1  c.c. 

1 
1 
1 
1 
1 

200 

400 
800 
1600 
3200 

03    °    0Q 

Jd| 

-On      a 
3t-  a 

0 

Complete  in  14  minutes. 
"  19 
"  52 
Incomplete. 

No    hemolysis     after     2 
hours. 

The  reason  for  the  poor  amboceptor  work  accomplished 
on  these  days  was  apparently  made  clear  by  the  foregoing 
standardization,  and,  as  a  result  of  this,  my  Wassermann 
work  is  now  performed  after  consulting  the  barometer,  and 
if  the  atmospheric  pressure  is  in  the  neighborhood  of  765, 
the  working  unit  is  doubled.  It  is  needless  to  emphasize 
the  fact  that  proper  controls  were  carried  on  while  making 
the  studies  of  the  low-power  amboceptor.  As  nearly  as 
possible  the  same  factors  entered  into  the  gaging  of  the 
amboceptor  during  both  clear  and  cloudy  days  with  a  high 
humidity.  It  is  extremely  vexing  to  be  called  upon  to  ex- 
plain a  positive  Wassermann  reaction  in  a  patient  who  does 
not  exhibit  the  slightest  sign  of  syphilis  nor  give  a  clue  in 
his  anamnesis;  for  this  reason  I  believe  it  is  much  safer  to 
gage  the  work  so  as  to  eliminate  all  possibilities  of  error  in 
this  direction,  even  if  thereby  one  reports  an  inordinate 
number  of  negative  results  on  known  syphilitic  subjects. 


SEROLOGY  65 

Of  this,  more  will  be  said  under  the  head  of  The  Attitude  of 
the  Serologist.  It  seems  to  me  that  the  peculiarity  of  the 
amboceptor  just  described  tends  to  corroborate  the  belief 
expressed  by  some  workers  that  the  entire  Wassermann 
reaction  is  simply  a  phenomenon  of  surface  tension.1  Before 
concluding  this  section  I  wish  to  add  another  point  regarding 
the  preservation  of  the  A.  S.  A.  Previous  to  placing  the 
serum  in  test-tubes  for  sealing,  it  is  advisable  to  add  to 
each  cubic  centimeter  of  the  immune  serum  some  tricresol 
solution  in  a  concentration  not  greater  than  1:2000.  It 
is  best  first  to  make  a  solution  of  the  preservative  in  salt 
solution  and  then  add  it  to  the  amboceptor.  This  will 
keep  the  serum  in  good  condition  for  many  months,  and 
do  away  with  the  unpleasant  odor  that  old  amboceptors 
usually  display.  A  sediment  will  always  develop,  but 
this  does  not  interfere  with  the  hemolytic  power  of  the 
serum. 

The  Preparation  and  Properties  of  the  Antigen. — The 
chief  argument  against  strict  conformance  to  the  side-chain 
theory  of  the  Wassermann  reaction  is  the  antigen.  The 
number  of  substances  that  can  be  used  for  the  purpose 
of  binding  complement  with  a  serum  containing  the  so- 
called  syphilitic  antibody  and  their  great  variability  all  tend 
to  prove  that  strict  specificity  is  not  a  part  of  the  test,  but, 
rather,  that  the  entire  reaction  is  more  or  less  a  fortunate 
coincidence  of  phenomena  of  which  little  has  as  yet  been 
incontrovertibly  established.  It  is  a  well-known  fact  that 
classic  inhibition  may  be  obtained  with  syphilitic  sera  using 
as  antigens  lecithin  (Porges  and  Meier)  or  the  salts  of  the 
bile  acids,  soaps,  etc.  (Sachs  and  Altmann),  and  other 
substances  mentioned  under  the  head  of  The  History  and 
Development  of  the  Wassermann  Reaction.  All  these  things 
tend  to  prove  that  the  antigenic  part  of  the  test  is  entirely 
a  matter  of  choice,  and  it  is  well  to  admit,  at  this  point,  that 
the  entire  usefulness  of  an  antigen,  or,  as  I  am  accustomed 
to  refer  to  it,  "the  inhibitory  extract,"  is  dependent  on  the 
carefulness  and  precision  with  which  the  extract  was  stand- 
ardized. The  finer  details  of  standardization  must  be  given 
1  G.  A.  Stephens:  Brit.  Med.  Jour.,  April  5,  1913,  pp.  697,  752. 
5 


66        SEROLOGY    OF    NERVOUS    AND    MENTAL    DISEASES 

close  attention  if  one  wishes  to  eliminate  non-specific  in- 
hibition and  avoid  the  humility  that  follows  incorrect 
reports.  The  only  property  that  one  expects  the  inhibitory 
extract  to  possess  is,  as  its  name  implies,  inhibition  of  he- 
molysis; specificity  is  of  secondary  consideration.  This  is 
perhaps  one  of  the  reasons  why  so  many  heterogeneous  sub- 
stances are  employed  as  inhibitory  extracts. 

Of  the  known  properties  of  the  antigen,  very  little  can 
be  said.  The  general  view  held  regarding  its  ability  to  bind 
complement  is  that  it  possesses  a  molecule  chemically  related 
to  lipoids,  which,  as  is  generally  known,  are  substances 
capable  of  producing,  under  certain  circumstances,  the  phe- 
nomenon of  complement  deviation.  Besides  this,  there  are 
other  very  interesting  and  important  facts  to  be  learned  from 
the  study  of  the  substances  used  as  antigens.  Those  who  use 
liver  extracts  have  observed  a  peculiar  wave  of  potentiality 
in  the  extract  in  the  course  of  time,  and  reported  very  good 
results  by  making  use  of  extracts  that  were  discarded  as 
having  become  too  weak,  and,  therefore,  useless  (Kaplan, 
Beneke,  Stuehmer).  The  last-named  author,  using  alcoholic 
extracts  from  guinea-pig  livers,  observed  the  following 
changes  in  them:  Extract  No.  I  was  not  treated  in  any 
way;  Extract  II  was  kept  for  twelve  hours  at  38°  C,  and,  of 
course,  was  decomposed  by  bacteria;  Extract  III  was  kept 
in  the  ice-chest  for  fourteen  days,  and  was  also  decomposed 
by  bacteria;  Extract  IV,  kept  for  nineteen  days  at  18°  C, 
was  decomposed  by  bacteria;  Extract  V,  kept  for  four 
weeks  in  the  ice-chest,  remained  sterile  and  dry.  The  vari- 
ous extracts  showed  the  following  properties: 

Quantity.  Ext.  I.  Ext.  II.  Ext.  III.  Ext.  IV-  Ext.  V. 

0.25  c.c a  a  d  a  a 

0.125  c.c b  b  b  a  a 

0.06  c.c c  b  a  a  a 

0.03  c.c d  c  a  a  a 

0.015  c.c d  d  a  a  b 

0.007  c.c d  d  a  a  c 

0.004  c.c d  d  a  a  d 

0.002  c.c d  d  b  b  d 

0.001  c.c d  d  d  c  d 

a  =  total  inhibition;  b  =  partial  inhibition;  c  =  incomplete* hemol- 
ysis;  d  =  complete  hemolysis. 


SEROLOGY  67 

To  estimate  the  inhibitory  strength  of  the  foregoing 
extracts  one  would  have  to  consider  the  size  of  the  dose  and 
the  result  following.  The  smallest  amount  of  extract  cap- 
able of  causing  inhibition  is  the  extract  most  suitable  for  the 
test.  In  the  preceding  analysis  it  is  evident  that  Extract 
IV  produced  complete  inhibition  with  only  0.004  c.c.  of  the 
extract.  Extracts  I  and  II  were  useless;  Extract  III,  al- 
though useful  in  the  smaller  doses,  was  hemolytic  to  start 
with;  Extract  V,  although  dry  and  sterile,  was  not  so  potent 
as  the  decomposed  Extract  IV.  I  was  able  to  demonstrate 
that  old  extracts,  after  having  been  discarded  on  account  of 
impaired  inhibitory  action,  were  found  to  possess  marked 
inhibitory  powers  a  few  weeks  later.  This  was  observed  a 
sufficient  number  of  times  to  make  careful  observations 
necessary  before  a  given  inhibitory  extract  is  discarded  as 
useless.  Some  authors  believe  that  the  extracts  used  for 
making  the  Wassermann  test  can  be  resolved  into  their 
different  components  by  appropriate  treatment:  U.  Fried- 
mann  demonstrated  that  the  hemolytic  component  of  the 
extract  is  soluble  in  water-free  ether;  F.  Lesser  found  the 
inhibitory  side-chain  (if  I  may  so  designate  it)  soluble  in 
ether.  Ehrmann  and  Stern  could  separate  the  inhibitory 
molecule  from  its  interfering  side-chains.  Joannowicz  and 
Pick  determined  later  that  the  unsaturated  fatty  acids  were 
responsible  for  the  hemolytic  qualities  of  the  extract,  while 
the  acetone-precipitable  lipoids  represented  the  inhibitory 
principle.  J.  Zeissler  observed  that  extracts  kept  on  ice 
for  four  weeks  lose  their  hemolytic  property,  whereas  the 
inhibitory  qualities  remain  intact.  All  these  observations 
suggest  the  complexity  of  the  inhibitory  extract  and  permit 
the  conception  that  the  antigen  in  the  Wassermann  reaction 
consists  of  a  complex  molecule  of  a  lipoid  nature,  with  an 
inhibitory  nucleus  and  a  number  of  side-chains,  some  of 
which  are  decidedly  hemolytic  in  character.  The  hemolytic 
side-chain  is  decomposed  in  a  comparatively  short  time,  a 
fact  that  enables  one  to  use  the  extract  again,  frequently  in 
a  smaller  dose  than  at  the  original  standardization.  These 
data  are  very  important  in  the  consideration  of  the  in- 
hibitory extract,  as  they  give  one  a  means  of  effecting  so- 


68        SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

called  restoration  of  the  useful  properties  it  has  lost.  Dia- 
grammatically,  the  entire  process  of  restoration  of  the 
inhibitory  power  may  be  pictured  as  follows: 


Neutral  Prolan 
Faff  y  acid  side  chain 


Hemolytic 
Properties 

Fig.  16. 


oE 


v~v 


Inhibitory 
Properties. 


As  the  protein  side-chain  undergoes  autolytic  decompo- 
sition or  bacterial  putrefaction,  the  fatty  acid  complex  is 
left  attached  to  the  lipoid  nucleus,  and  the  balance  of  power 
is  in  favor  of  hemolysis;  such  an  extract  is  useless.  In  the 
course  of  time  further  decomposition  takes  place,  and  the 
fatty  acid  side-chain  no  longer  interferes  with  the  lipoid 
inhibitory  nucleus.  Although  greatly  decomposed  and 
malodorous,  such  treatment  frequently  gives  powerful  in- 
hibitory extracts  in  remarkably  small  doses.  These  changes, 
of  course,  take  place  in  watery  extracts  only,  the  alcoholic 
extracts  not  being  affected  by  bacteria  and  but  very  little 
by  autolysis.  Regarding  the  preparation  of  antigens,  one 
may  use  either  the  watery  or  the  alcoholic  organic  extracts, 
as  he  desires.  In  this  work  the  various  methods  will  be 
described,  together  with  such  observations  as,  in  the  writer's 
experience,  were  found  of  practical  value,  the  object  being 
to  render  the  Wassermann  reaction  less  difficult  and  more 
attractive. 

Preparation  of  the  Watery  Luetic  Fetal  Liver  Extract. — 
A  number  of  luetic  fetal  livers  are  weighed  and  finely  com- 
minuted. To  each  gram  of  tissue  4  c.c.  of  0.9  NaCl  solution 
are  added;  to  this  is  further  added  a  sufficient  quantity  of 
phenol  to  make  a  0.5  per  cent,  solution.  This  is  placed  in  a 
dark   container    (an   Erlenmeyer  flask  covered  with  black 


SEROLOGY  69 

paper),  tightly  stoppered,  and  vigorously  shook  in  a  shaking 
machine  for  twenty-four  hours.  I  use  the  Spiegelberg 
apparatus,  but  any  other  instrument  will  answer  provided 
the  flask  can  be  so  placed  as  to  prevent  accidents  overnight. 
Next  day  the  entire  mass  is  centrifuged  and  the  coarser 
particles  discarded.  The  opalescent  supernatant  fluid  is 
the  syphilitic  antigen  as  prepared  by  Wassermann.  This 
fluid  is  placed  in  a  dark,  rubber-stoppered  bottle,  and  left 
in  the  ice-chest  ready  for  use.  In  order  to  avoid  contamina- 
tion it  is  advisable  to  pipet  off  the  amount  to  be  used  for  the 
day,  and,  without  exposing  the  bottle  to  sunlight,  replace  it 
in  the  ice-chest.  With  proper  precautions,  in  my  experience, 
such  extracts  can  be  used  for  months  and  retain  their  full 
strength.  In  America  the  question  of  obtaining  luetic  livers 
is  attended  with  great  difficulties,  a  fact  the  reason  for  which 
I  am  unable  to  state. 

In  order  to  render  the  extract  less  changeable,  Marie  and 
Levaditi  suggest  the  method  of  pulverizing  the  luetic  liver 
which  has  been  dried  in  vacuo.  This  retains  its  inhibitory 
qualities  remarkably  well,  and  can  be  used  until  the  last 
grain  is  exhausted.  It  is  prepared  by  mixing  the  powder 
with  salt  solution  in  the  proportion  of  1:4  and  extracted 
for  twenty-four  hours.  The  suspension  is  centrifuged,  and 
the  supernatant  fluid  is  ready  for  use. 

Of  the  alcoholic  tissue  antigens,  the  following  are  to  be 
recommended:  Landsteiner,  Mueller,  and  Poetzl  rub  up  to 
a  fine  consistence  the  muscular  parts  of  guinea-pig  hearts, 
and  extract  1  gm.  of  this  with  50  c.c.  of  95  per  cent,  alco- 
hol at  60°  C.  for  several  hours.  This  mixture  is  filtered,  and 
the  filtrate  preserved  in  this  state  at  room  temperature. 
Michaelis  and  Lesser  rub  up  in  a  mortar  syphilitic  or  normal 
livers,  and  shake  the  mass  at  once,  for  five  or  six  hours,  with 
10  parts  its  weight  of  alcohol.  After  standing  for  twenty- 
four  hours  the  clear,  supernatant  fluid  is  pipeted  off  and  kept 
in  the  ice-chest  as  the  stock  solution.  For  use  they  dilute 
1  part  of  the  stock  solution  with  4  parts  of  physiologic 
salt  solution. 

Noguchi's  method  of  preparing  the  acetone  insoluble  anti- 
gen is  as  follows:   Extract  finely  minced  syphilitic  or  normal 


70        SEROLOGY    OF    NERVOUS   AND    MENTAL   DISEASES 

liver  with  10  volumes  of  95  per  cent,  alcohol  for  about  a 
week,  at  a  temperature  of  37°  C.  At  the  end  of  this  time  filter 
the  alcohol  and  evaporate  the  filtrate  by  using  a  fan  at  a 
temperature  of  less  than  40°  C.  This  sometimes  requires 
twenty-four  hours  or  more.  The  residue  is  extracted  with 
ether  and  permitted  to  evaporate.  The  residue  of  the 
ethereal  extract  is  taken  up  with  a  small  quantity  of  ether 
and  fractionated  with  5  volumes  of  acetone.  A  sticky, 
gummy  precipitate  forms,  which  adheres  to  the  stirring  glass 
rod.  Pour  off  the  supernatant  acetone,  permitting  the 
remainder  to  evaporate.  Collect  the  resinous  mass  into  a 
dark  bottle,  and  keep  it  air  tight  in  the  ice-chest.  For  mak- 
ing the  test  0.2  gm.  is  dissolved  in  a  little  ether  and  brought 
up  to  100  c.c.  with  0.9  per  cent.  NaCl  solution.  This  emul- 
sion can  be  kept  on  ice  without  impairing  its  inhibitory 
qualities. 

In  my  laboratory  I  use  the  following  method :  Guinea-pig 
hearts  are  weighed  and  minced  in  a  meat-mincer.  The 
entire  mass,  plus  bloody  fluid,  is  placed  in  a  dark  bottle, 
and  ten  times  the  volume  of  95  per  cent,  alcohol  added. 
This  is  kept  in  the  incubator  at  37°  C.  and  shaken  twice 
daily  for  four  days.  To  this  alcoholic  extract  cholesterin  is 
added,  thus:  Four  grams  of  Merck's  cholesterin  are  dis- 
solved in  as  little  ether  as  possible  and  added  to  96  c.c.  of 
the  alcoholic  extract  of  guinea-pig  hearts.  This  makes  a 
turbid  fluid  which,  on  standing  in  the  ice-chest,  deposits 
cholesterin  at  the  bottom  of  the  container.  For  use  the  mix- 
ture is  shaken  and  placed  in  the  thermostat  at  56°  until  the 
cholesterin  dissolves,  and  1.5  c.c.  are  brought  up  to  100  c.c. 
with  0.9  NaCl  solution.  In  my  work  1  c.c.  of  this  solution 
will  inhibit  syphilitic  sera,  but  is  not  in  the  least  inhibitory 
with  non-luetic  material.  I  have  also  used  the  watery  ex- 
tract of  syphilitic  fetal  livers  whenever  possible,  preparing 
it  according  to  the  method  of  Wassermann. 

It  is  immaterial  what  one  uses  for  antigen,  so  long  as  the 
substance  conforms  to  the  requirements  of  the  reaction,  i.  e., 
to  inhibit  with  luetic  sera  and  not  to  interfere  with  he- 
molysis when  the  serum  is  not  luetic.  This  question  is  set- 
tled by  the  standardization  of  a  given  extract. 


Fig.  17.— The  Wassermann  reaction,  showing  at  the  top  the  heap  of 
cells  which  is  significant  of  complete  inhibition  of  haemolysis.  Test- 
tube  1  is  the  positive  control  of  the  reaction,  and  the  others  represent 
complete  haemolysis  of  the  remaining  controls  of  the  reaction. 


SEROLOGY 


71 


Standardization  of  an  Extract  to  Be  Used  as  Antigen. — 

Known  syphilitic  serum,  0.2  c.c;  complement,  0.1  c.c;  to 
this  add  extract  in  varying  strengths;  incubate  at  37°  C.  for 
one  hour;  add  1  c.c.  of  sheep  cells  (well  washed  and  made 
up  to  5  per  cent,  with  0.9  NaCl  solution) ;  add  two  units  of 
amboceptor,  and  note  the  time  when  hemolysis  takes  place 
in  the  tubes  with  the  smallest  amount  of  extract.  If  the 
extract  is  at  all  serviceable,  then  it  ought  to  show  complete 
inhibition  with  at  most  0.2  c.c  of  the  extract.  If  it  requires 
a  greater  amount  to  produce  inhibition,  the  extract  will 
most  likely  become  useless  in  less  than  a  week.  The  same 
procedure  is  repeated  with  a  normal  serum.  In  my  labora- 
tory the  previously  described  antigen  with  cholesterin  rein- 
forcement gave  the  following  titer: 


Positive  Series. 

Negative  Series.1 

Amount  of  Extract. 

Inhibition. 

Inhibition. 

0.6  c.c. 
0.4  c.c. 
0.2  c.c. 

Complete 

It 
it 

Slight 

Very  slight 

None 

0.1  c.c. 

<< 

u 

0.05  c.c. 

tt 

<< 

0.025  c.c. 

tt 

tt 

0.0125  c.c. 
0.00625  c.c. 

Incomplete 
Hemolysis 

tt 

The  above  antigen  showed  the  ability  to  inhibit  with 
syphilitic  serum  in  the  0.025  dose,  whereas  by  using  0.2  c.c 
with  the  normal  serum  no  inhibition  was  obtained.  The 
rationale  of  the  antigenic  standard  is  admirably  conformed 
with  in  the  foregoing  extract.  Any  substance  that  will  in- 
hibit completely  with  a  positive  serum  in  a  dose  that  is  not 
potent  enough  to  do  the  same  with  a  normal  serum,  even  if 
the  dose  is  three  times  larger,  fulfils  the  requirements  of  an 
antigen  for  performing  the  Wassermann  reaction.  This 
practically  covers  the  entire  principle  of  antigenic  activity 


1  The  same  quantities  were  used  as  in  the  positive  series.    Normal 
sera  were  used,  otherwise  everything  as  before. 


72        SEROLOGY   OF   NERVOUS   AND    MENTAL   DISEASES 

as  applied  to  the  practical  Wassermann  laboratory  method. 
Manifold  theoretic  considerations  enter  in  the  modus 
operandi  of  antigens,  but  these  do  not  concern  the  practical 
worker,  who  is  interested  only  in  the  clinical  side  of  the 
question. 

Various  Inhibitory  Substances  Used  as  Antigens. — Aside 
from  the  use  of  non-luetic  organic  extracts  for  complement 
deviation  tests  in  syphilis,  other  substances  of  known  chem- 
ical constitution  were  made  use  of.  Schuermann's  method 
of  preparing  such  an  antigen  is  as  follows:  Lecithin,  0.3  gm. 
dissolved  in  50  c.c.  of  absolute  alcohol;  sodium  glycero- 
phosphate, 0.3  gm.  in  5  c.c.  of  0.9  per  cent.  NaCl  solution. 
Of  this  solution,  30  c.c.  are  mixed  with  5  c.c.  of  lactic  acid 
and  10  c.c.  of  ammonium  vanadinate.  The  unit  is  established 
according  to  the  standardizing  schedule  previously  outlined. 
Porges  and  Meier  make  a  1  per  cent,  solution  of  lecithin 
(Kahlbaum),  shaking  it  in  0.5  per  cent,  phenol-normal  salt 
solution,  which  serves  as  a  stock  solution.  With  0.05  c.c.  of 
this  solution  most  luetic  sera  inhibit  and  non-luetic  sera 
hemolyze.  This  antigen  is  not  to  be  recommended  for 
practical  work,  as  the  margin  of  error  on  the  positive  side 
is  too  great  for  clinical  purposes. 

Sachs  and  Rondoni  give  the  following  formula  for  a  useful 
antigen: 

Sodium  oleate  (Kahlbaum) 2.5 

Ovolecithin  (Merck) 2.5 

Oleic  acid  (Kahlbaum) 0.75 

Distilled  water 12.5 

Alcohol,  95  per  cent ad  1000.0 

For  use,  the  foregoing  is  mixed  thoroughly  with  0.9  per 
cent.  NaCl  solution  in  the  proportion  of  one  part  of  the 
extract  to  five  of  the  salt  solution.  The  usefulness  of  an 
extract  depends  entirely  upon  the  results  of  the  standardiza- 
tion; this  is  chiefly  the  distance  between  the  complete  in- 
hibitory dose  with  positive  sera  and  the  non-inhibition  with 
normal  material.  The  greater  this  distance,  the  better  the 
extract,  and  the  fewer  the  errors  that  will  be  obtained  by  its 
use. 


various  modifications  of  wassermann  reaction    73 

The  Various  Modifications  of  the  Wassermann 
Reaction 

In  America  the  Noguchi  modification  is  used  quite  exten- 
sively. The  presence  of  a  natural  anti-sheep  amboceptor  in 
some  human  sera  resulted  in  many  negative  results  with 
some  unquestionable  syphilitic  sera.  To  overcome  this 
difficulty  Noguchi  devised  the  method  of  using  human 
blood-corpuscles  and  a  corresponding  amboceptor  for  the 
indicator,  instead  of  the  anti-sheep  system,  as  in  the 
original  Wassermann  reaction.  This  method  is  to  be 
recommended  especially  when  it  is  difficult  to  obtain  sheep 
cells  in  a  fresh  state.  Noguchi  uses  the  acetone-insoluble 
fraction  of  beef  livers  as  his  antigen.  The  blood  for  the 
work  can  be  obtained  from  the  patient's  finger.  Only  a  few 
drops  are  necessary.  The  entire  contents  of  the  test-tube, 
after  the  addition  of  all  the  reagents,  amount  to  about  1.5 
c.c.  A  water-bath  is  required  for  the  fixation  and  for  the 
hemolytic  incubation.  So  far  as  results  with  this  method 
are  concerned,  I  can  state,  after  having  performed  4200 
comparative  Wassermann  and  Noguchi  reactions,  that  the 
latter  is  slightly  simpler  than  the  Wassermann  reaction. 
The  transference  of  the  reagents  to  paper  I  do  not  consider 
an  advantage,  but  rather  a  drawback.  It  is  my  belief  that, 
by  furnishing  the  reagents  to  laboratory  workers,  they 
are  deprived  of  the  benefit  of  the  experience  to  be  gathered 
by  gaging  them,  and  is  decidedly  detrimental  to  obtaining 
correct  Wassermann  results.  The  sending  of  antigen  and 
amboceptor  paper  to  different  workers,  thereby  making 
it  easy  for  them,  and  reducing  the  Wassermann  test  to  a 
mere  throwing  together  of  bits  of  paper,  is  not  to  be  recom- 
mended. I  believe  that  Noguchi  has  given  up  the  saturation 
of  paper  strips,  and  now  recommends  the  use  of  definite 
amounts  of  fluid  reagent.  All  things  being  equal,  the  reac- 
tion is  fairly  reliable,  and  in  my  hands  gave  a  positive  error 
of  2.5  per  cent. 

Another  modification  is  the  Bauer  test.  This  author 
omits  the  making  and  the  standardization  of  the  A.  S.  A., 
and  relies  entirely  upon  the  natural  anti-sheep  amboceptor 
present  in  the  serum  of  the  patient.    This  is  a  very  unreliable 


74        SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

and  uncertain  method,  as  the  natural  A.  S.  A.  is  not  always 
present  in  a  serum. 

The  Tschernogouboff  method  omits  still  more  reagents, 
dispensing  with  complement  as  well  as  with  amboceptor. 
This  observer  uses  the  natural  amboceptor  and  the  com- 
plement in  the  patient's  serum,  against  guinea-pig  ery- 
throcytes, neglecting  entirely  the  quantitative  relationship 
of  the  reaction.  The  same  can  be  said  of  the  Hecht  modi- 
fication, which  does  not  differ  from  that  suggested  by  Tscher- 
nogouboff. 

Margarete  Stern  adds  a  quantity  of  anti-sheep  ambocep- 
tor to  the  active  serum  of  the  patient  (not  heated  at  56°  C), 
and  omits  the  guinea-pig  complement.  As  the  complement 
in  human  serum  is  a  very  inconstant  ingredient,  and  is,  on 
an  average,  much  less  potent  than  the  guinea-pig  serum, 
this  modification  also  has  its  drawbacks. 

Detre  and  Brezovsky  used  an  anti-horse  system.  Boas 
recommended  an  anti-goat  system.  Browning  employed  an 
anti-ox  hemolytic  amboceptor. 

Some  time  after  the  Noguchi  method  appeared,  Tscherno- 
gouboff also  devised  an  anti-human  method  similar  to  that 
of  his  predecessor.  The  latter's  observations,  however, 
lack  the  elaborateness  of  those  of  the  Japanese  worker,  and 
the  method  is  also,  for  other  reasons,  less  reliable. 

Close  upon  the  trail  of  the  Wassermann  publications 
appeared  a  number  of  reactions  that  did  not  depend  upon 
the  phenomenon  of  complement  deviation,  but  upon  other 
physicochemical  laws.  Porges  and  Meier  elaborated  a 
method  of  precipitation,  using  0.2  c.c.  of  a  1  per  cent,  stock 
suspension  of  lecithin;  to  this  they  add  1  c.c.  of  a  1:5  solu- 
tion of  the  patient's  serum  in  0.9  per  cent.  NaCl  solution. 
This  mixture  is  placed  in  thin  precipitation  tubes  and  left 
in  the  incubator  for  a  few  hours.  These  authors  report  a 
faintly  positive  result  whenever  a  finely  granular  opacity 
takes  place  in  the  tube.  If  a  sediment  is  obtained  in  twenty- 
four  hours,  then  the  reaction  is  considered  as  positive;  a 
total  precipitation  of  the  lecithin  mixture  is  considered  as 
strongly  positive.  As  this  reaction  is  obtainable  with  ad- 
vanced tuberculosis,  in  tumors,  lepra,  trypanosomiasis,  and 


THE    CONTROLS   AND   THEIR   SIGNIFICANCE  75 

even  occasionally  in  absolutely  healthy  individuals,  it  is 
not  to  be  recommended  as  a  test  to  be  depended  upon 
alone,  without  the  use  of  the  original  Wassermann  reaction. 

A  later  study  by  Porges  and  Salomon  advocates  the  use 
of  a  1  per  cent,  sodium  glycocholate  (Merck)  solution  in  dis- 
tilled water.  The  solution  is  mixed,  in  equal  parts,  with  an 
absolutely  clear,  inactivated  portion  of  the  patient's  serum. 
This  is  placed  in  test-tubes  of  about  7  mm.  inner  diameter, 
which  are  large  enough  to  hold  0.2  c.c.  of  each  substance. 
The  tubes  are  permitted  to  remain  undisturbed  at  room 
temperature.  If  the  serum  is  syphilitic,  distinct  flocculi 
will  appear  at  the  top  of  the  fluid.  Opalescence  and  the 
presence  of  traces  of  flocculi  are  not  conclusive.  As  precau- 
tions, the  following  suggestions  are  offered:  Do  not  form 
layers,  as  such  treatment  permits  of  the  formation  of  rings. 
Incubation  temperature  is  conducive  to  the  development  of 
bacteria.  The  solution  must  be  freshly  prepared.  The 
addition  of  phenol  renders  the  reaction  less  specific.  The  use 
of  turbid  or  hemoglobin-containing  sera  interferes  with  the 
test.  The  end  reaction  is  to  be  observed  with  the  naked 
eye  and  by  ordinary  light. 

The  water  reaction  of  Klausner  is  performed  as  follows: 
Into  a  test-tube  of  5  mm.  inner  diameter  and  7  cm.  high 
place  0.2  c.c.  of  the  patient's  serum,  which  must  be  abso- 
lutely clear  and  blood  free;  this  is  diluted  with  0.6  c.c.  of 
distilled  water.  In  a  few  hours — rarely  more  than  fifteen — 
one  notices,  in  luetic  sera,  a  thick  sediment.  The  more 
florid  the  lues,  the  sooner  does  sedimentation  take  place. 
After  treatment  a  previously  positive  reaction  may  become 
negative. 

The  Controls  and  Their  Significance 
The  absence  of  standards  and  definite  quantitative 
chemical  relations  requires  the  use  of  many  controls  in 
place  of  more  exact  procedures.  It  is  necessary  that  the 
serologist  be  able  to  draw  upon  a  mass  of  known  material 
for  his  controls,  otherwise  his  work  is  rendered  very 
difficult  indeed.  The  positive  control  serves  as  an  index 
of  the  antigen's  potency,  and,  as  its  name  implies,  is  ob- 


76        SEROLOGY   OF   NERVOUS   AND   MENTAL  DISEASES 

tained  from  a  known  syphilitic  with  a  positive  Wasser- 
mann  reaction.  For  the  selection  of  such  a  serum  it  is  not 
advisable  to  make  use  of  a  patient  who  is  "Wassermann 
fast"  (see  Wassermann-fast  tabes),  as  these  subjects  react 
quantitatively  with  much  less  antigen  than  does  the  ordi- 
nary positive  luetic,  which  quantity,  when  used  on  ordinary 
material,  will  result  in  a  series  of  negative  Wassermanns  even 
on  manifestly  positive  sera.  To  recapitulate:  The  positive 
control  contains  the  ordinary  positive  serum  plus  the  half 
unit  of  antigen,  plus  the  complement,  and,  after  the  pre- 
liminary binding  incubation,  plus  the  sheep  cells  and  two  or 
three  units  of  amboceptor. 

The  negative  control  is  intended  to  guard  against  too  large 
doses  of  antigen  and  partly  also  against  too  small  quantities 
of  amboceptor.  For  such  purposes  jaundiced  sera,  as  well 
as  lipemic  sera,  are  not  to  be  used.  The  same  ingredients  as 
above,  with  the  exception  that  the  serum  be  negative,  are 
placed  in  the  test-tube  as  before. 

The  amboceptor  control  corresponds  with  the  ambocep- 
tor titration,  as  suggested  by  Citron,  and  serves  to  elimin- 
ate an  amboceptor  dose  that  is  too  weak  for  hemolytic  pur- 
poses. The  test-tubes  in  actual  work  contain  complement 
and  salt  solution  to  start  with,  and  after  the  preliminary 
incubation  cells  and  the  amount  of  amboceptor  determined 
for  the  day  are  added.  The  control  for  antigenic  interference 
is  to  determine  whether  the  quantity  of  the  extract  is  not 
too  great,  and  whether  it  is  capable  of  inhibiting  hemolysis 
without  the  addition  of  the  patient's  serum.  The  tubes 
contain  all  the  material  except  the  patient's  serum.  The 
auto-inhibition  control  is  the  most  important  one  of  the 
series.  Some  sera,  although  negative,  are  very  slow  in 
hemolyzing,  and  it  is,  therefore,  not  advisable  to  read  end- 
results  before  the  auto-inhibition  control  is  completely 
cleared,  i.  e.,  shows  total  absence  of  inhibition.  The  test- 
tube  containing  this  control  contains  all  the  material  except 
the  antigen,  and  serves  to  eliminate  the  not  infrequent 
anticomplementary  sera.  On  days  when  the  barometer  is 
at  765,  the  auto-inhibition  controls  are  more  frequently  un- 
hemolyzed  than  on  other  days. 


PLATE 


§  g* 

<*-  s 
°i 
sa 

a  cs 
o>    _ 

on  ^ 

0>  eT 




U 

c 

•a 

01 

fl 

bl 

z 

a 

<rt 

— 1 

> 

0) 

> 

fl 

^- 

,fl 

_= 

> 

fi 

c 

o 

a 

— 

y 

- 

r, 

> 

o 

— i 

- 

+= 

a) 

> 

si 

■_ 

m 

in 

:.. 

d 

a 

cS 

a 

a 

b: 

- 

r> 

(3 

GO 

J4 

£a 


-2   o 

-£3  a  >» 

S  rt  a 

CO  O 


THE    PERFORMANCE    OF   THE    WASSERMANN    REACTION      77 

In  the  colored  illustration  test-tube  No.  1  represents  the 
positive  control,  and,  as  shown,  is  the  only  positive  non- 
hemolyzed  test  in  the  rack.  All  the  other  test-tubes  are 
clear,  as  they  should  be  in  a  properly  controlled  reaction. 
The  only  test  that  must  be  repeated  with  every  serum  is 
the  auto-inhibition  control;  otherwise  the  remaining  controls 
serve  for  any  number  of  reactions. 

The  Performance  of  the  Wassermann  Reaction 

As  a  rule,  the  serologist  begins  his  collection  of  sera  for 
the  Wassermann  reaction  on  the  day  before  the  test  is  to 
be  made.  The  blood  is  collected  in  an  ordinary  test-tube 
and  placed  at  room  temperature,  to  permit  the  coagulum 
to  express  the  serum.  The  clear  serum  is  collected  in  smaller 
tubes  and  appropriately  labeled,  and  placed  in  the  ice-chest 
until  the  next  day.  On  the  day  before  the  test  is  to  be  made 
all  the  utensils  that  may  come  in  contact  with  the  serum 
should  be  sterilized.  A  large-sized  guinea-pig  is  exsan- 
guinated, with  the  precautions  described  under  comple- 
ment, and  left  overnight  at  room  temperature. 

The  first  task  on  the  following  morning  is  to  obtain  sheep 
blood  and  rid  it  of  its  adherent  serum.  This  requires  three 
or  four  washings  with  salt  solution. 

The  next  step  is  to  collect  the  complement  in  a  sterile 
centrifuge  tube,  and  if  there  are  traces  of  blood,  it  is  neces- 
sary to  centrifuge  the  serum.  Having  obtained  the  washed 
cells  and  the  complement,  the  standardization  of  the  ambo- 
ceptor is  begun.  The  method  previously  described  in  this 
section  is  to  be  followed  exactly.  Having  standardized  and 
ascertained  the  size  of  one  unit,  the  next  thing  to  do  is  to 
place  all  the  sera  in  the  thermostat  at  a  temperature  not 
above  56°  C.  The  sheep  cells  are  next  diluted  to  a  5  per 
cent,  suspension  with  0.9  per  cent,  of  NaCl  solution;  to  this 
suspension  is  added  an  equal  quantity  of  salt  solution  con- 
taining 3  to  4  units  of  amboceptor  to  each  cubic  entimeter 
of  salt  solution.  The  4  unit  dose  of  amboceptor  is  to  be 
used  on  days  when  the  barometer  is  near  765.  The  method 
of  ascertaining  the  antigen  unit  is  the  one  described  on 
p.  71,  and  is  to  be  so  diluted  that  each  cubic  centimeter 


78        SEROLOGY    OF   NERVOUS    AND    MENTAL  DISEASES 

of  salt  solution  contains  half  a  unit  of  the  inhibitory  ex- 
tract. 

After  three-quarters  of  an  hour's  inactivation  at  56°  C. 
the  various  sera  to  be  analyzed  are  removed  from  the  ther- 
mostat, and  disposed  of  as  follows: 

1.  Place  in  each  of  two  tubes,  front  and  back,  0.2  c.c.  of 
the  patient's  serum. 

2.  Add  to  each  tube  0.1  c.c.  of  the  guinea-pig  comple- 
ment. 

3.  To  the  front  tube  only  add  1  c.c.  of  the  antigen,  which 
equals  half  a  unit  as  ascertained  in  the  standardization. 

4.  Bring  up  the  mixture  in  each  tube  to  3  c.c.  with  0.9 
NaCl  solution. 

5.  Place  the  rack  with  the  tubes  into  the  thermostat  at 
37°  C,  having  previously  shaken  each  test-tube.  The 
incubation  for  complement  binding  should  last  one  hour. 

6.  After  one  hour  add  to  each  tube,  front  and  back,  2 
c.c.  of  the  blood-amboceptor  mixture,  and  after  thoroughly 
shaking,  replace  in  incubator  for  the  hemolytic  incubation. 
From  now  on  every  tube  must  be  closely  examined  every  ten 
to  fifteen  minutes.  As  soon  as  the  tubes  in  the  controls,  with 
the  exception  of  the  positive  control,  have  hemolyzed,  the 
negative  sera  are  recorded  and  removed  from  the  incubator. 
This  gives  the  eye  less  work  in  running  over  the  entire  series 
of  tests,  especially  when  the  number  of  bloods  to  be  tested 
is  great.  Only  those  sera  that  remain  unhemolyzed  to  the 
end  of  the  process,  and  even  until  the  next  day,  should  be 
regarded  as  positive.  The  serologist  should  not  attempt  to 
give  weakly  positive  reports  or  make  use  of  misleading  terms, 
such  as  four  plus,  three  plus,  or  plus-minus.  Patients  either 
have  or  have  not  a  positive  Wassermann,  and  all  other 
designations  tend  to  render  the  situation  more  complex  and 
uncertain  to  the  serologist  and  more  so  to  the  clinician. 

The  Wassermann  reaction  on  the  cerebrospinal  fluid  is  per- 
formed in  the  same  way  as  the  serum  reaction,  except  that 
the  fluid  is  not  inactivated.  The  use  of  larger  quantities  of 
fluid  is  permissible  only  as  a  therapeutic  guide,  and  should 
never  be  considered  as  a  reliable  index  for  the  existence  of  a 
syphilitic  neurologic  disorder  when  the  result  is  positive  with 


THE    PERFORMANCE    OF    THE    WASSERMANN   REACTION      79 

quantities  greater  than  that  which  is  used  in  the  performance 
of  the  original  Wassermann  reaction.  With  large  quantities 
of  fluid,  using  as  much  as  1  c.c,  one  may  at  times  obtain 
positive  results  in  non-luetic  individuals,  and  subject  the 
patient  unnecessarily  to  therapeutic  measures  that  are  un- 
called for  and  will  do  him  no  good.  This  method  will  be 
discussed  further  under  the  head  of  Syphilitic  Neurologic 
Disorders. 

The  Attitude  of  the  Serologist. — Every  serologist  learns, 
sooner  or  later,  that  no  matter  how  conscientious  his  work- 
ing methods  are,  a  number  of  errors  cannot  be  avoided  with 
the  Wassermann  reaction,  and  that  some  of  the  positive 
reports  submitted  were  unquestionably  on  negative  mate- 
rial. He  must,  therefore,  accept  the  inevitable,  and  come 
to  regard  the  entire  test  as  only  of  secondary  importance  in 
making  a  complete  study  of  a  case  of  syphilis.  The  sooner 
the  serologist  arrives  at  this  point  of  wholesome  skepticism, 
the  better  for  his  reports,  as  only  then  will  they  contain  the 
information  desired — i.  e.,  is  the  reaction  negative  or  posi- 
tive? 

This  is  practically  all  the  physician  requires  to  know;  the 
explanations  and  fanciful  designations  of  the  end-result  are 
absolutely  unwarranted.  There  are  some  workers  who 
pride  themselves  on  their  ability  to  report  a  positive  Wasser- 
mann on  every  syphilitic  serum.  In  my  experience,  the  un- 
erring positive  is  always  accompanied  by  a  long  list  of 
positive  reports  on  distinctly  non-syphilitic  patients.  This 
is  amply  illustrated  by  the  many  defenses  advanced  by 
serologists  who  never  err  in  their  recognition  of  luetic  sera, 
by  their  ingenious  logic  in  explaining  how  syphilis  could 
be  overlooked  clinically,  how  the  disease  could  remain 
latent  or  obscure,  when  their  unerring  positive  reaction  is 
obtained  on  a  patient  free  from  lues.  It  is,  therefore,  quite 
important  to  be  acquainted  with  the  private  views  of  the 
serologist  as  to  the  significance  he  places  on  the  Wasser- 
mann reaction,  as  to  his  opinion  of  his  results  in  the  reaction, 
whether  absolute  perfection  is  attainable  in  this  test,  etc. 
I  believe  that  the  attitude  of  the  serologist  is  a  greater  factor 
in  the  value  of  a  Wassermann  reaction 'than  is  the  standard- 


80        SEROLOGY   OF   NERVOUS   AND    MENTAL    DISEASES 

ization  of  the  reagents.  The  question  of  reliability  resolves 
itself  into  this:  a  worker  reports  either  too  many  positive 
Wassermann  reactions  in  non-syphilitic  persons,  or  too 
many  negative  reactions  in  those  who  were  infected.  Unless, 
therefore,  the  serologist  determines  on  which  side  he  intends 
to  err,  his  results  will,  accordingly,  be  uncertain. 

The  function  of  the  laboratory  is  not  to  diagnosticate 
syphilis;  its  duty  is  to  report  the  results  of  a  test-tube  ex- 
periment that  has  only  a  certain  amount  of  specificity. 
Syphilis  should  never  be  diagnosed  in  the  laboratory,  nor 
should  the  laboratory  worker  consider  himself  competent  to 
give  the  final  decision.  It  will,  therefore,  be  necessary  for 
the  investigator  to  so  arrange  his  working  reagents  that  only 
those  sera  will  be  reported  upon  as  positive  that  have  with- 
stood every  attempt  at  negativation.  Of  course,  it  is  pos- 
sible to  add  so  much  of  the  amboceptor  that  even  the  posi- 
tive serum  of  a  patient  with  general  paresis  will  eventually 
hemolyze.  It  is  my  experience  that  many  weakly  positive 
reactions  are  due  simply  to  the  use  of  too  weak  reagents, 
such  as  a  poor  (too  old)  complement,  or  the  using  of  the 
Citron  method  of  standardizing  the  amboceptor  and  of  em- 
ploying only  two  units.  Using  too  much  of  the  inhibitory 
extract  is  another  factor  in  the  production  of  weakly  positive 
results  or  positive  reactions  on  non-luetic  patients.  The 
reading  of  end-results  must  take  into  consideration  all  these 
points,  and  allowance  must  be  made  for  the  atmospheric 
pressure  and  meteorologic  conditions.  The  careful  worker 
will,  therefore,  in  the  course  of  time,  consider  a  serum  as 
positive  only  when  it  has  resisted  all  the  attempts  at  nega- 
tivation just  described — i.  e.,  the  use  of  three  or  four  ambo- 
ceptor units,  the  employment  of  only  one-half  or  even  one- 
third  of  the  inhibitory  unit,  the  selection  of  vigorous  animals 
for  the  complement,  etc.  It  is  absolutely  necessary  for  the 
reliability  of  at  least  the  positive  Wassermann  that  the 
serologist  should  entirely  disregard  diagnostic  responsibili- 
ties and  merely  submit  the  results  of  his  test-tube  analyses. 
He  should  frankly  admit  his  mistake  when  a  positive  report 
is  given  on  a  non-syphilitic  individual,  and  not  defend  his 
results  by  the  arguments  previously  mentioned  here.     He 


THE    PERFORMANCE    OF   THE    WASSERMANN    REACTION      81 

should  make  every  attempt  to  negativate  sera,  and  only 
when  this  is  impossible  should  he  report  that  a  given  serum 
is  positive.  By  assuming  this  attitude  I  was  enabled  to 
report  correct  positive  Wassermann  results  in  all  but  0.3  per 
cent,  of  positive  results.  The  0.3  per  cent,  were  errors,  as 
pointed  out  by  the  clinicians  who  treated  the  patients  in 
question.  The  percentage  of  negative  reports  in  syphilitic 
sera  was  naturally  very  large;  nevertheless,  when  the  number 
of  recently  treated  syphilitics,  as  well  as  cases  of  old,  quies- 
cent tabes,  is  deducted  from  this  list,  the  percentage  of 
such  reports  is  reduced  to  about  7  of  the  entire  number  of 
syphilitic  sera. 

In  submitting  a  serum  for  analysis  it  is  important,  in  order 
to  obtain  an  unbiased  opinion  from  the  laboratory,  to  with- 
hold the  clinical  findings  in  the  case.  The  factor  of  personal 
equation  is  a  very  great  one  in  reading  end-results,  and  often 
influences  the  serologist  to  report  as  weakly  positive,  sera 
that  would  have  been  considered  as  negative  had  the  serol- 
ogist been  unaware  of  the  physician's  opinion  in  the  case. 
Of  still  greater  significance  is  it  to  keep  the  laboratory  in 
absolute  ignorance  of  the  clinical  facts  during  the  per- 
formance of  scientific  investigations  with  the  Wassermann 
reaction,  as  the  results  from  such  premature  knowledge  are 
entirely  derogatory  to  the  reliability  of  the  serologist's 
conclusions;  it  is  absolutely  impossible,  in  such  instances, 
to  leave  personal  equation  entirely  out  of  consideration. 
The  possession  of  clinical  facts  previous  to  rendering  results 
in  a  series  of  Wassermann  reactions,  as  offered  by  some  work- 
ers on  the  subject  of  specificity,  or  the  introduction  of  new 
methods,  makes  the  results  of  the  research  much  less  valu- 
able than  if  the  same  work  were  conducted  independently  of 
such  clinical  knowledge.  It  is  my  advice,  therefore,  to  those 
who  wish  to  engage  in  experimental  work,  to  reject  all  in- 
formation that  might  interfere  with  the  rendition  of  an 
unbiased  and  reliable  conclusion.  If  this  rule  had  been 
adopted  before  some  reports  were  submitted  the  results 
would  have  been  entirely  different;  biased  opinion  in  these 
cases  can  be  excluded  with  a  fair  degree  of  certainty. 

The  average  serologist  is  oftentimes  unable  to  differentiate 

6 


82        SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

between  an  incomplete  reaction,  which  should  not  be  re- 
ported upon  as  positive,  and  the  unquestionable,  complete 
inhibition;  in  such  a  case  the  majority  of  laboratory  workers 
will  report  positive  findings  instead  of  performing  the  test, 
as  Zeissler  suggested,  with  less  serum,  or,  as  I  am  accus- 
tomed to  do,  use  more  amboceptor.  The  desire  to  detect 
as  many  syphilitic  sera  as  possible  and  thereby,  so  to  say, 
show  an  increase  in  his  efficiency,  makes  the  serologist  with 
a  moderate  experience  commit  many  avoidable  errors;  such 
a  worker,  if  he  is  in  possession  of  facts  suggestive  of  syphilis, 
is  really  afraid  to  report  as  negative  the  findings  in  such  a 
patient,  with  the  result  that  many  innocent  persons  are 
made  to  carry  the  burden  of  a  supposed  infection,  and, 
besides,  are  subjected  unnecessarily  to  antiluetic  medication. 
It  cannot  be  denied  that  many  individuals  today  carry  the 
stigma  of  syphilis  as  the  result  of  a  superficial  examination 
made  by  a  physician  before  the  days  of  the  Wassermann 
reaction.  It  is  to  be  deplored  that  today  such  occurrences  are 
not  only  not  diminished,  but  are  actually  increased,  as  a  re- 
sult of  the  serologist's  attitude  toward  the  Wassermann  test. 
Attempts  have  been  made  to  increase  the  sensitiveness  of 
the  test  by  using  methods  that  are  calculated  not  to  make 
the  number  of  negative  findings  greater,  but,  on  the  con- 
trary, to  make  the  number  of  positives  as  great  as  possible; 
the  fact  that  the  number  of  innocent  sufferers  is  also  in- 
creased is  not  considered.  Such  methods  are  the  result  of 
laboratory  overzealousness  and  insufficient  clinical  knowl- 
edge. The  work  of  Noguchi,  although  excellent  from  the 
standpoint  of  the  laboratory  expert,  is  sadly  lacking  in  those 
clinical  qualities  that  make  the  method  he  elaborated  as 
useful  as  he  would  like  to  have  it.  The  same  can  be  said 
regarding  the  "Auswertungs  Methode"  of  Hauptmann,  who, 
in  order  to  avoid  the  possibility  of  reporting  as  negative 
specific  cerebrospinal  fluids,  uses  quantities  so  large  that  a 
positive  result  is  eventually  obtained  in  some  non-specific 
fluids. 

The  chief  function  of  the  laboratory  worker,  in  my  opinion, 
is  not  so  much  to  detect  every  syphilitic,  but  to  protect  the 
non-luetic  individual  from  a  wrong  diagnosis  and  useless 


THE   PERFORMANCE   OF   THE    WASSERMANN   REACTION      83 

treatment.  It  should  be  the  duty  of  every  serologist  to 
do  his  utmost  to  secure  results  that  are  characteristic  of 
the  unequivocal  positive  Wassermann,  and  he  should  con- 
sider himself  as  expert  only  when  the  number  of  positive 
reports  on  non-luetic  sera  approaches  the  zero  mark,  and 
not  when  his  results  with  positive  material  approach  the 
100  per  cent,  efficiency  mark.  As  previously  stated,  there 
are  no  two  ways  of  performing  and  rendering  results  with 
the  Wassermann  reaction — either  one  is  erring  on  the  posi- 
tive side,  or  commits  the  greatest  number  of  mistakes  on  the 
negative  side,  and  the  latter  is  by  far  the  lesser  evil  of  the 
two.  Clinicians  ought  to  acquaint  themselves  with  the 
views  of  the  serologist  before  placing  any  confidence  in  his 
results.  In  concluding  this  very  important  section  I  would 
warn  the  clinician  against  the  unerring  serologist;  in  the 
present  state  of  our  knowledge  of  immunoserology  such 
workers  are  a  menace  to  physicians  and  patients. 


PART 


THE    SEROLOGY    OF    NERVOUS    AND    MENTAL 
DISEASES  OF  NON-LUETIC  ETIOLOGY 

GENERAL  CONSIDERATIONS 

Non-syphilitic  nervous  and  mental  diseases  have  no  di- 
rect connection  etiologically  with  the  spirochetes  of  syphilis. 
Although  a  patient  with  any  one  of  the  neurologic  affections 
may  have  come  in  contact  with  syphilis  either  prenatally 
or  postnatally,  it  is  universally  conceded  that  the  disease  in 
question  is  not  syphilitic,  although  it  may  be  argued  that 
lues  may  have  played  a  part  as  a  predisposing  factor.  What- 
ever its  relation  to  the  diseases  mentioned  below,  antiluetic 
therapy  plays  no  very  important  role  in  their  amelioration 
or  eradication.  This  statement  applies  only  to  those  cases 
whose  serum  and  cerebrospinal  fluid  display  a  persistent 
negative  Wassermann  reaction;  where  the  anamnesis  and 
the  physical  examination  reveal  luetic  manifestations, 
antiluetic  measures  are,  of  course,  to  be  undertaken.  On 
the  other  hand,  one  must  not  lose  sight  of  the  possibility 
of  a  coexistent  lues  of  the  viscera  in  a  patient  with  any  one 
of  the  acceptedly  non-luetic  diseases  of  the  nervous  system. 

From  a  clinical  point  of  view,  the  differentiation  requires 
great  analytic  experience,  as  well  as  a  sound  consideration 
of  the  serologic  data;  it  suffices  here  to  mention  the  co- 
existence of  lues  in  a  profound  neurasthenic  or  in  a  patient 
with  multiple  sclerosis,  in  which  cases  it  may,  perhaps,  be 
excusable  to  think  of  general  paresis  in  the  former,  and  of 
cerebrospinal  lues  in  the  latter.  That  there  are  fine  points  of 
differentiation  in  both  conditions  one  must  admit;  also 
that  there  are  some  cases  in  which  even  careful  and  ex- 
perienced clinicians  have  failed  to  establish  definitely  the 


MENINGEAL    AFFECTIONS  85 

nature  of  the  malady.  The  purpose  of  the  following  ex- 
position of  the  serology  of  non-luetic  nervous  and  mental 
diseases  is  to  give  to  the  clinician  additional  means  whereby 
errors  may  be  eliminated  by  the  performance  of  a  series  of 
tests  which,  together  with  the  clinical  findings,  will  complete 
the  bedside  and  the  laboratory  picture  of  a  given  disease. 
At  the  conclusion  of  each  clinical  picture  the  serology  of 
the  disease  as  found  in  the  majority  of  instances  will  be 
given;  this  serologic  picture  will  be  designated  as  the  "average 
formula."  For  the  sake  of  brevity  the  Wassermann  reaction 
will  be  designated  as  W.  R.;  the  globulin,  as  Gl.;  the  cell 
count,  as  PI.  (pleocytosis) ;  Fehling's  reduction,  as  Feh.  If 
normal  or  absent,  the  minus  sign  (—  )  will  be  used;  if  present 
or  in  excess,  the  plus  sign  (+)  will  be  employed.  In  the 
case  of  Fehling's  reduction,  the  presence  of  an  excess  of 
reducing  substance  (glucose?)  will  be  tabulated  as  +  +  . 
This  will  also  apply  to  a  marked  excess  of  globulin  and  to  a 
hyperlymphocytic  cell  count.  Instead  of  the  word  "serum," 
S.  will  be  used,  and  C.  S.  F.  will  represent  the  cerebrospinal 
fluid. 

MENINGEAL  AFFECTIONS 

Micotic   Meningitis  "With   Demonstrable  Bacteria  in 

the  Fluid 

Epidemic  Cerebrospinal  Meningitis. — That  this  form  of 
meningitis  is  caused  by  the  organism  known  as  Weichsel- 
baum's  diplococcus,  and  that  the  pneumococcus  of  Frankel 
is  not  a  causal  factor  in  epidemics  of  the  disease,  are  accepted 
by  most  authorities.  The  serology  of  the  acute  form  shows 
a  marked  increase  in  the  cellular  content  of  the  spinal  fluid, 
which  may  number  several  thousand  to  the  cubic  millimeter, 
and  may  even  be  so  abundant  as  to  make  an  actual  count 
without  great  dilution  impossible.  The  cells  show  great 
variety,  with  a  large  percentage  of  polynuclears,  and  the  fluid 
is  often  purulent.  The  globulin  is  greatly  in  excess,  and  may 
be  obtained  in  a  fluid  diluted  1:10.  Other  protein  bodies 
are  also  present,  and  are  demonstrable  by  suitable  chemical 
methods.  The  reduction  of  the  Fehling  solution  is  absent, 
as  a  rule. 


86        SEROLOGY    OF   NERVOUS   AND    MENTAL   DISEASES 

It  is  advisable  for  the  serologist  to  come  to  the  patient 
prepared  to  inject  any  of  the  remedies  in  use.  The  efforts 
of  Wassermann-Kolle,  Lepine,  Jochmann,  Flexner,  Schoene, 
and  others  have  placed  at  the  disposal  of  the  clinician  im- 
mune substances  capable  of  influencing  this  very  fatal  affec- 
tion. As  no  time  must  be  lost,  and  the  patient's  serious 
condition  must  be  considered,  the  serum  should  be  in- 
jected as  soon  as  the  diagnosis  is  corroborated  by  the  micro- 
scope; hence  the  advice  just  given,  to  be  prepared  with  every- 
thing necessary  for  the  purpose.  In  a  case  in  which  I  was 
called  into  consultation  the  equipment  consisted  of  a  micro- 
scope, staining  fluids,  counting  chamber,  75  c.c.  of  Flexner's 
antimeningitic  serum,  and  a  lumbar  puncture  needle.  As 
no  lymphocytosis  was  obtained,  the  fluid  was  not  injected. 
An  interesting  study  of  this  subject  was  made  by  Sophian 
in  a  recent  epidemic.  Average  formula :  S. :  W.  R.  —  ; 
C.  S.  F.:  W.  R.  -  ;  Gl.  +  +  ;  PI.  +  +  ;  Feh.  -  . 

Influenza  Meningitis. — In  two  cases  of  this  disease  I  found 
the  typical  organism  described  by  Pfeiffer.  There  was  a 
moderate  lymphocytosis  in  both  instances,  with  an  excess 
of  protein.  Fehling's  solution  was  not  reduced  in  one  case, 
whereas  the  other  gave  a  prompt  reduction.  The  fluid  that 
did  not  reduce  the  Fehling  solution  showed  82  polynuclear 
cells  to  the  c.mm.,  besides  167  lymphocytes.  The  poly- 
nuclear content  of  the  other  was  very  low,  showing  only  3 
polynuclears  to  the  cubic  millimeter.  Average  formula: 
S.:  W.  R.  -  ;  C.  S.  F.;  W.  R.  -  ;  Gl.  +;  PI.  +;  Feh.  +. 

Diphtheric  Meningitis. — Bonhoff,  Leede,  and  others  were 
able  to  demonstrate  the  Klebs-Loffler  bacillus  in  meningitis 
accompanying  diphtheria.  Aside  from  the  presence  of  the 
bacterium,  the  other  meningitic  laboratory  manifestations 
were  also  demonstrable:  globulin  excess,  pleocytosis,  dimin- 
ished reducing  substance,  increased  pressure. 

Gonococcic  Meningitis. — The  gonococcus  may  invade  the 
meninges.  The  literature  contains  observations  made  by 
Furbringer,  Deposse,  de  Josselin  de  Jong,  and  a  few  others, 
who  found  the  gonococcus  in  the  cerebrospinal  fluid.  That 
the  gonococcus  resembles  the  meningococcus  of  Weichsel- 
baum  very  closely  is  true,  and  one  may  with  justification 


Fig.  18. — Protein  excess  as  observed  in  a  case  of  acute  meningitis. 
Author's  method,  showing  an  excess  in  the  tube  containing  0.2  c.c.  of 
cerebrospinal  fluid  and  0.3  c.c.  of  water  The  last  tube,  with  only  0.1  c.c, 
also  presents  a  faint  ring. 


MENINGEAL    AFFECTIONS  87 

question  the  genuineness  of  the  observation;  on  the  other 
hand,  I  have  heard  the  opinion  expressed  by  an  authority 
whose  judgment  in  such  matters  carries  great  weight,  that  a 
certain  meningomyelitic  process  was  of  gonococcic  origin, 
this  remark  having  been  made  after  opening  the  dura  and 
making  a  study  of  the  contents  of  the  dural  sac. 

Typhoid  and  Paratyphoid  Meningitis. — A  genuine  menin- 
gitis caused  by  either  the  typhoid  or  paratyphoid  micro- 
organism is  a  possibility,  although  a  rare  one.  Lenhartz, 
Silberberg,  Hugot,  Boden,  and  others  reported  the  finding 
of  these  bacilli  in  the  cerebrospinal  fluid.  It  does  not  neces- 
sarily follow  that  the  meningeal  symptoms  frequently  en- 
countered in  these  diseases  are  the  result  of  a  micotic  menin- 
gitis; the  irritation,  as  will  be  pointed  out  further  on,  is,  in  the 
majority  of  instances,  a  reflex  one,  if  one  may  be  permitted 
to  use  the  term  in  connection  with  a  meningeal  response  to  a 
general  infection  without  being  itself  {%.  e.,  the  meningeal 
structure)  attacked  by  the  bacilli. 

Tuberculous  Meningitis. — This  form  of  meningitis  is 
always  secondary  to  a  focus  existing  elsewhere,  although 
during  life,  and  even  at  the  postmortem  examination,  the 
primary  lesion  may  not  be  found.  The  serology  of  this  dis- 
ease is  characterized  by  the  presence  of  a  lymphocytosis  which 
may  be  very  pronounced,  or  may  be  accompanied  by  an  ex- 
ceedingly small  number  of  cells.  When  the  condition  is 
present  in  pure  form,  one  usually  finds  the  lymphocyte; 
when  there  is  a  mixed  infection,  the  presence  of  polynuclear 
elements  is  demonstrable.  In  the  case  of  a  mixed  infection, 
it  is  possible  to  estimate  the  extent  of  the  inflammatory 
process  by  the  number  of  polynuclear  elements.  As  the  men- 
ingitis subsides  the  polynucleosis  also  tends  to  diminish, 
and  the  previously  absent  Fehling's  reducing  substance 
gradually  returns. 

A  pure  lymphocytosis  in  a  child  should  always  suggest  a 
tuberculous  meningitis,  and  a  diligent  search  for  tubercle 
bacilli  should  be  undertaken.  With  the  milder  forms  of 
this  disease  the  protein  content  is  not  markedly  increased, 
whereas  a  marked  excess — up  to  a  1 : 5  dilution — is  obtainable 
in  the  severer  forms,  particularly  where  a  mixed  infection  is 


88        SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

present.  The  search  for  the  tubercle  bacillus  frequently  con- 
sumes much  time,  and  in  the  end  the  bacillus  may  escape 
detection.  Some  writers  claim  to  have  found  this  organism 
in  over  90  per  cent,  of  their  cases  of  tuberculous  meningitis, 
a  fact  not  borne  out  by  my  own  experience. 

According  to  Trembur,1  it  is  possible  to  increase  the  num- 
ber of  tubercle  bacilli  in  a  given  tuberculous  fluid  by  sub- 
jecting the  obtained  fluid  to  an  incubation  temperature  for 
twenty-four  hours,  all  precautions  against  contamination 
having  been  observed.  The  number  may  be  so  largely  aug- 
mented that  one  can  obtain  without  difficulty  one  or  two 
good  specimens  from  every  six  or  seven  fields. 

Mestrezat  lays  great  stress  on  the  fact  that  the  meninges 
in  tuberculous  meningitis  present  a  greater  permeability  to 
nitrates  than  does  any  other  meningeal  involvement.  He 
gives  the  patient  1  gram  of  sodium  nitrate  for  every  30 
kilos  of  body-weight,  and  analyzes  the  fluid  three  hours 
after  the  ingestion  of  the  salt.  In  the  normal  state  the 
amount  of  sodium  nitrate  obtained  in  the  fluid  ranges  from 
8  to  10  milligrams  per  liter.  The  amount  obtained  after 
the  ingestion  of  1  gram  of  the  salt  may  vary  1  or  2  milli- 
grams normally.  In  case  of  tuberculous  meningitis,  the 
quantity  obtained  may  be  anywhere  from  40  to  85  milli- 
grams. His  tables  show  that  after  ingestion  of  the  salt 
in  any  other  form  of  meningitis  the  augmentation  in  the 
amount  of  nitrates  in  the  fluid  is  strikingly  small,  as  may 
be  seen  from  the  following  examples: 

Clinical  Diagnosis.  Milligrams     of     Sodium 

Nitrate  Found  in  the 
Fluid. 

Tabes  (6  cases) 9  to  13 

Arteriosclerosis  (2  cases) 12  to  14 

Cerebellar  glioma 8 

Cerebral  congestion 10 

Syphilitic  paraplegia 18 

Multiple  sclerosis 15 

Tuberculous  meningitis  (9  cases) 43  to  85 

Syphilitic  meningo-encephalitis  (semi-coma)  40  to  45 

Cerebrospinal  meningitis 38 

In  one  case  of  this  disease  Hauptmann,  using  the  "Aus- 
wertungs  Methode,"  obtained  a  positive  Wassermann  reac- 
1  Trembur:    Klin.  Jahrbuch,  No.  24 


MENINGEAL   AFFECTIONS  89 

tion;  this  is  to  be  considered  as  a  result  of  the  use  of  larger 
quantities  of  fluid  than  are  employed  in  the  Wassermann 
school ;  the  possibility  of  syphilis  as  a  factor  in  its  production 
may  be  an  argumentative  subject,  but  cannot,  in  view  of  the 
clinical  facts  of  the  case,  be  considered.  Average  formula: 
S.:  W.  R.  -  ;  C.  S.  F.:  W.  R.  -  ;  Gl.  +;  PI.  +;  Feh.  +. 

Pneumococcic  Meningitis.— In  a  case  in  which  I  had  the 
opportunity  to  analyze  the  fluid  showing  this  coccus,  the 
cell  count  showed  84  lymphocytes  per  c.mm.  and  8  poly- 
nuclear  cells;  the  protein  content  showed  a  1  to  3  ex- 
cess, and  the  Fehling's  reduction  was  prompt.  This  form  of 
meningitis  is  not  uncommon.  Average  formula:  S.:  W.  R. 
-  ;  C.  S.  F.:  W.  R.  -  ;  Gl.  +;  PI.  +;  Feh.  +. 

Meningitis  of  Otic  Origin. — The  presence  of  a  meningitis 
in  a  purulent  otitis  media  is  not  always  to  be  demonstrated 
by  lumbar  puncture.  When  found,  however,  it  adds  an 
element  of  danger  which  greatly  complicates  the  treatment, 
as  well  as  rendering  the  prognosis  much  more  grave.  The 
severity  of  the  meningitis  is  dependent  upon  the  patho- 
genicity of  the  causal  microorganism.  As  a  rule,  the  infection 
that  follows  an  otitis  is  usually  a  mixed  one.  On  the  other 
hand,  it  is  not  rare  to  have  a  serous  meningitis  as  a  result 
of  ear  suppuration.  The  serology  in  such  a  case  is  usually 
negative,  or  may  be  accompanied  by  an  increase  in  protein 
without  an  accompanying  lymphocytosis.  Some  cases  im- 
prove spontaneously  after  the  lumbar  puncture,  a  point  that 
may  be  utilized  in  the  therapy  of  such  cases  (A.  Bruce). 
Although  the  presence  of  pus  and  bacteria  in  the  fluid  ob- 
tained by  lumbar  puncture  is  significant  in  itself,  it  never- 
theless does  not  help  us  to  differentiate  between  meningitis 
and  brain  abscess.  The  performance  of  lumbar  puncture 
in  otic  complications  is  not  devoid  of  danger.1 

The  fluid  usually  contains  cells  and  bacteria,  and  is  turbid ; 
this  occurs,  of  course,  only  when  the  communication  between 
the  cavity  of  the  skull  and  the  spinal  canal  is  open,  which  is 
not  always  the  case. 

The  consensus  of  opinion  of  aurists  is  divided  on  the  sub- 
ject of  lumbar  puncture:    some  would  employ  it  for  diag- 
1  Grunert:   Munch,  med.  Woch.,  1905. 


90        SEROLOGY   OF    NERVOUS    AND    MENTAL   DISEASES 

nostic  purposes  in  every  instance;  whereas  others  would 
resort  to  it  only  in  cases  where  the  differential  diagnosis  de- 
mands it.  Average  formula:  S.:  W.  R.  -  ;  C.  S.  R:  W.  R. 
-;G1.  +;P1.  +  +  ;Feh.  -. 

Staphylococcus  Meningitis. — The  Staphylococcus  aureus 
or  albus  may  be  the  exciting  cause  in  this  form  of  meningitis. 
The  condition  is  observed  usually  after  injuries  to  the  skull 
or  during  the  course  of  sepsis.  On  the  whole,  it  is  a  very 
rare  form  of  infection,  and  is  demonstrable  only  by  careful 
cultural  methods.  One  rarely  finds  the  coccus  in  the  smear 
preparation.  When  the  opportunity  for  growth  and  prop- 
agation is  favorable,  the  coccus  may  then  be  observed  in 
the  smear.  The  remaining  serology  is  the  usual  meningitic 
pleocytosis,  globulin  excess,  etc. 

Streptococcic  Meningitis. — This  form  of  meningitis  is 
generally  secondary  to  a  streptococcic  invasion  elsewhere. 
In  the  case  of  the  Streptococcus  erysipelatis,  the  meningitis 
develops,  as  a  rule,  after  one  or  more  of  the  cranial  sinuses 
have  become  involved.  The  meningeal  reaction  is  very 
severe,  and  goes  hand  in  hand  with  the  clinical  manifesta- 
tions, as  well  as  with  spinal  fluid  changes.  In  the  strepto- 
coccic varieties  of  meningitis  are  to  be  found  the  most  puru- 
lent spinal  fluids. 

Plaut  described  a  Streptococcus  mucosus  which  was  first 
seen  by  Bonome.  According  to  the  former  observer,  small 
epidemics  of  this  form  of  meningitis  were  observed  by  him, 
the  mortality  ranging  from  40  to  50  per  cent.  In  the  sporadic 
forms  of  this  disease  the  meningitis  was  secondary  to  an 
otitis  media  purulenta.  Of  these  cases,  every  one  proved  to 
be  fatal.  The  microorganism  was  demonstrable  in  the 
spinal  fluid,  and,  besides  showing  the  usual  characteristics 
of  an  acute  purulent  meningitis,  the  cell  count  in  one  in- 
stance showed  30,720  cells  per  cubic  millimeter,  of  which 
90  per  cent,  were  polynuclear  elements.  The  streptococci 
capsules  are  seen  in  the  smear,  and  appear  in  long  chains, 
visible  in  every  portion  of  the  preparation. 

The  Streptococcus  putridus  was  demonstrated  in  the 
spinal  fluid  as  a  secondary  invasion  from  a  focus  in  the  ear, 
and  in  another  instance  in  the  course  of  puerperal  sepsis. 


MENINGEAL    AFFECTIONS  91 

The  nature  of  the  streptococci,  with  the  possible  exception 
of  the  Streptococcus  mucosus,  is  best  demonstrated  by 
culture. 

Remarks. — Besides  the  micotic  invaders  just  mentioned, 
various  authors  have  reported  the  finding,  in  the  cerebro- 
spinal fluid  of  the  Bacillus  coli  commune;  the  Bacillus  pyo- 
cyaneus;  the  Bacillus  mallei;  the  Bacillus  anthracis;  the 
saccharomyces  and  the  actinomyces. 

In  all  forms  of  micotic  meningitis  the  disease  process 
may  be  confined  to  a  very  small  area,  giving  rise  to  local 
manifestations  only.  If  the  process  is  well  excluded  from 
the  general  meningeal  area  and  from  the  channels  through 
which  abnormal  elements  find  their  way  into  the  spinal 
fluid,  one  may  not  observe  marked  changes  in  the  fluid.  Of 
course,  an  excess  of  globulin  may  be  demonstrated,  but  even 
this  may  be  lacking  if  the  meningitis  is  in  the  frontal  region, 
very  small  in  extent,  and  well  encapsulated.  These  circum- 
scribed forms  of  meningitis  may  frequently  escape  labora- 
tory recognition  on  one  occasion,  and  at  a  subsequent  punc- 
ture may  manifest  all  the  signs  of  a  meningitic  process, 
the  result,  most  likely,  of  the  extension  of  the  process  or  of 
the  breaking  down  of  the  protective  barriers. 

If  the  protective  barrier  breaks  down,  one  no  longer  deals 
with  a  circumscribed  disease,  and  the  bacterium  becomes 
apparent  either  culturally  or  in  the  smear.  The  latter  find- 
ing marks  the  existence  of  a  diffuse  cerebrospinal  meningitis. 
The  terms  "pseudomeningitis"  and  "meningismus"  do  not 
convey  the  necessary  information,  and  are  only  misleading; 
equally  meaningless  is  the  term  "meningitis  sine  meningitide" 
(Fr.  Schultze).  We  are  justified  in  distinguishing  between 
the  diffuse  and  the  circumscribed  forms  of  meningitis  mi- 
cotica,  and  I  consider  the  absence  of  an  accepted  meningitic 
serology,  such  as  a  pathologic  pleocytosis,  globulin  excess, 
etc.,  as  the  distinguishing  feature  between  the  circum- 
scribed and  the  diffuse  forms  of  this  disease.  The  presence 
of  these  manifestations,  and,  above  all,  the  finding  of  the  ex- 
citing microorganism,  remove  the  disease  from  the  class 
of  the  circumscribed  meningitides. 


92      serology  of  nervous  and  mental  diseases 

Non-micotic  Meningitis 

Secondary  Meningitis  or  Meningitis  Serosa. — In  contra- 
distinction to  meningitis  micotica  we  have  meningitis  serosa. 
The  cellular  increase  in  the  cerebrospinal  fluid  in  the  course 
of  a  typhoid  that  presents  meningeal  manifestations  is  due 
most  likely  to  a  meningitis  of  this  form.  The  bacteria  are 
not,  of  course,  demonstrable  in  the  fluid.  A  general  staphy- 
lococcus infection  or  certain  infective  endocarditides  give 
rise  to  a  serous  meningitis.  Other  infectious  diseases  may 
also  cause  an  increase  in  the  number  of  cells  in  the  cerebro- 
spinal fluid  without  demonstrating  the  bacterium  responsible 
for  the  increase.  In  cases  in  which  it  is  absolutely  necessary 
to  differentiate  between  the  infectious  fever  and  the  cause 
of  the  meningitis  careful  cultural  methods  of  examining  the 
blood  and  the  spinal  fluid  are  the  only  means  by  which  light 
is  shed  on  the  subject.  In  the  presence  of  a  positive  blood- 
culture  in  a  patient  with  an  infectious  disease  showing  men- 
ingeal complications,  the  absence  of  the  bacterium  from  the 
cerebrospinal  fluid  is  generally  sufficient  to  establish  the 
diagnosis  of  a  meningitis  serosa  (non-micotica) . 

It  seems  to  me  that  further  subdivision  of  the  subject  is 
only  conducive  to  error,  and  I  will,  therefore,  include  under 
the  heading  of  Non-micotic  Meningitis  or  Meningeal  Irri- 
tations all  those  conditions  that  are  capable  of  giving  rise  to 
abnormalities  in  the  cerebrospinal  fluid,  regardless  of  the 
fact  that  the  irritation  may  have  been  transmitted  through 
the  wall  of  a  bone  cavity,  without  the  actual  inflammatory 
process  coming  in  contact  with  the  meninges.     This  will 
give  us  the  meningitis  serosa  encountered  during  the  course 
of  an  otitis  media,  frontal  sinus  disease,  or  disease  of  any  of 
the  cavities  of  the  bones  of  the  skull.    The  fluid  is  often- 
times altered  but  little,  and  at  other  times  may  give  rise  to  a 
pathologic  cell  count.    The  globulin  is  but  rarely  in  excess, 
and  Fehling's  reduction  is  always  prompt.     Besides  these 
factors,   there   are   also   a  number  of  vascular  and  other 
brain  and  cord  manifestations  capable  of  producing  sufficient 
irritation  to  give  rise  to  the  above  serologic  changes.     Of 
these,  sinus  thrombosis  and  brain  abscess,  as  well  as  tumors, 


MENINGEAL   AFFECTIONS  93 

are  to  be  mentioned.  The  appearance  of  a  cellular  increase 
in  the  cerebrospinal  fluid  is  dependent  upon  a  number  of 
factors,  irrespective  of  the  cause  that  has  produced  the 
secondary  meningeal  manifestations.  If  the  iter  from  the 
irritating  focus  to  the  subarachnoid  space  and  into  the 
intradural  canal  is  clear  and  uninterrupted,  one  will  find 
various  cellular  elements  in  numbers  corresponding  to  the 
degree  of  irritation.  If  adhesions  exist,  or  even  if  a  thick 
layer  of  brain  tissue  intervenes,  then  a  pleocytosis,  even  of 
moderate  degree,  will  hardly  be  found.  A  tumor  or  a  deep 
cerebral  abscess  in  the  frontal  region  will  rarely  give  rise  to 
abnormalities;  a  similar  condition  in  the  pontocerebellar 
angle  will  frequently  give  abundant  evidence  of  the  presence 
of  an  irritation.  If  the  meningeal  irritation  is  very  severe, 
one  will  find,  besides  a  pathologic  cellular  increase,  also  a 
marked  protein  excess,  and  at  times  even  a  fibrinous  network, 
a  phenomenon  encountered  usually  in  acute  meningitis. 

Pleocytosis  as  a  response  to  an  irritation  is  to  be  con- 
sidered as  one  of  the  earliest  manifestations  in  the  course  of 
repair,  and  hence  may  be  regarded  as  the  first  attempt  by 
nature  to  guard  against  a  spreading  of  the  noxious  process. 
The  preponderance  of  phagocytic  elements  (polynuclear 
cells)  serves  as  an  index  to  the  degree  of  irritation.  The 
milder  forms  of  irritation  show,  as  a  rule,  only  few  poly- 
nuclear cells,  the  proportion  of  the  latter  increasing  as  the 
irritating  process  gains  in  extent  and  intensity.  Hence  the 
presence  of  cells  in  a  larger  number  than  normal  is  alone  suffi- 
cient to  serve  as  a  danger-signal  that  something  is  wrong 
somewhere  with  the  meninges.  In  treating  various  cerebro- 
spinal conditions,  the  disappearance  of  the  pleocytosis  is 
also  the  surest  index  of  the  success  of  the  treatment. 

This  dictum  is  true  of  all  cases,  with  the  single  exception  of 
tumors  of  the  spinal  cord.  In  the  latter  the  presence  of  a 
large  amount  of  protein  and  the  absence  of  a  corresponding 
pleocytosis  would  tend  to  show  that  the  protein  bodies 
found  are  chiefly  specific  tumor  proteins,  secreted  by  the 
tumor  cells  themselves.  It  is  certainly  very  difficult  to  ex- 
plain the  absence  of  cells  if  the  protein  excess  is  accepted 
only  as  a  meningeal  response 


94        SEROLOGY   OF    NERVOUS   AND    MENTAL    DISEASES 

Meningitis  serosa  is  at  times  differentiated  with  difficulty 
from  the  circumscribed  variety  of  micotic  meningitis. 
Perhaps  the  absence  of  manifestations  in  any  of  the  cavities 
of  the  bones  of  the  skull,  together  with  meningeal  signs  in 
the  course  of  an  infectious  disease,  ought  to  be  significant 
guides  in  the  establishment  of  a  serous  meningitis,  provided 
careful  cultural  methods  gave  no  evidence  of  the  presence 
of  a  bacterium.  It  is  extremely  important  for  the  surgeon, 
in  particular,  to  be  able  to  differentiate  between  a  circum- 
scribed meningitis  micotica  and  a  meningitis  serosa,  as  in 
the  former  condition  surgical  interference  may  result  in 
spreading  the  focus  of  infection,  with  the  resultant  general 
involvement  of  the  meninges. 

Hypertrophic  Laminated  Spinal  Meningitis. — In  one 
patient,  previous  to  making  the  lumbar  puncture,  the  diag- 
nosis was  tuberculous  meningitis,  being  based  on  the  signs 
at  his  apices  and  the  gibbus  in  the  dorsal  column.  The  symp- 
toms were  so  classic  that  only  as  a  last  resort  was  rachicentesis 
performed  at  the  suggestion  of  the  surgeon  who  subsequently 
operated  upon  the  patient.  The  result  of  the  rachicentesis 
was  very  striking,  in  that  it  gave  no  pleocytosis;  in  fact,  not 
one  cell  was  seen  in  the  centrifuged  specimen.  The  striking 
feature  was  the  marked  excess  of  protein  matter,  which 
congealed  with  heat  into  an  albumin  reaction.  The  presence 
of  a  possible  tumor  suggested  itself,  and  the  operation  re- 
vealed a  long  plastic  growth  or,  rather,  what  seemed  to  be 
a  neoplastic  formation.  The  specimen  submitted  for  ex- 
amination showed  a  tough,  fibrous  structure,  which,  even 
to  the  unaided  eye,  appeared  to  be  finely  laminated.  The 
microscopic  examination  showed  very  few  cellular  elements. 

Pachymeningitis  Haemorrhagica  Interna. — In  this  condi- 
tion the  chief  manifestation  is  the  tinge  of  the  cerebrospinal 
fluid,  which  is  sometimes  yellow  or  pinkish.  The  cellular 
elements  are,  as  a  rule,  not  striking;  here  and  there  an  old 
red  cell,  more  or  less  crenated  and  otherwise  distorted,  may 
be  found  in  the  fluid. 

In  cases  where  an  abnormal  (border-line)  count  is  obtained, 
one  may  also  detect  a  slight  globulin  excess. 


BRAIN    DISEASES  95 

BRAIN  DISEASES 

Cerebral  Hemorrhage. — Although  classified  under  the 
head  of  non-luetic  diseases,  syphilis  is  by  no  means  rarely 
present  in  vascular  affections  of  the  brain.  Depending 
upon  the  proximity  of  the  bleeding  vessel  to  the  ventricles  to 
the  subarachnoid  space,  and  to  the  iter  e  tertio  ad  quartum 
ventriculo,  blood  elements  will  be  found  in  the  spinal  fluid. 
It  is  remarkable  how  little  interference  will  produce  cellular 
alterations  in  the  cerebrospinal  fluid;  in  fact,  it  seems  that 
the  first  manifestation  of  an  abnormal  condition  is  the 
appearance  of  small  cells  in  the  fluid,  with  the  exception 
of  processes  producing  very  gradual  compression  of  the 
spinal  cord.  In  the  latter,  the  non-appearance  of  cells  in  the 
majority  of  instances  is  justly  considered  as  paradoxic. 
In  old  brain  hemorrhages  some  investigators  have  demon- 
strated the  presence  of  chemical  constituents  in  the  blood. 
The  presence  of  these  elements  is,  in  my  experience,  an  ex- 
ceptional finding,  as  the  majority  of  fluids  do  not  give 
chemical  blood  reactions  in  old  hemorrhages,  although  some 
cells  may  show  deposits  of  blood-pigment.  Fresh  blood 
constituents  may  find  their  way  into  the  cerebrospinal 
circulation,  with  the  proviso  noted  above.  An  excess  of 
globulin  is  but  rarely  encountered,  no  matter  what  method 
of  detection  is  employed.  If  it  is  present,  syphilis  is,  perhaps, 
the  causal  factor  in  its  appearance.  In  the  ordinary  simple 
arteriosclerotic  hemorrhage  of  advanced  age,  the  globulin 
content  is,  as  a  rule,  normal.  The  serology  of  the  serum  may 
be  positive  or  negative,  and  may  or  may  not  have  any  con- 
nection with  the  process  responsible  for  the  hemorrhage. 
It  is  quite  different  when  a  positive  Wassermann  is  obtained 
in  the  cerebrospinal  fluid,  a  result  that  invariably  indicates 
that  the  vascular  disease  is  a  syphilitic  one.  Where  the 
Wassermann  is  positive  in  the  spinal  fluid,  cells  are  also 
present,  while  a  globulin  excess,  with  ordinary  methods,  may 
be  absent.  The  Lange  method  of  using  colloidal  gold  for  the 
precipitation  of  globulin-like  substances  in  luetic  diseases 
of  the  central  nervous  system  will  give  the  reaction  of  an 
excess  more  often  than  the  usual  Nonne-Apelt,  Noguchi, 


96        SEROLOGY    OF    NERVOUS   AND    MENTAL   DISEASES 

Ross,  or  Kaplan  methods.  The  reduction  of  the  Fehling 
solution  is  prompt  in  every  instance  of  brain  hemorrhage. 
Average  formula:  S.:  W.  R.  —  or  + ;  C.  S.  F.:  W.  R.  —  or 
+  ;  Gl.-;  Pl.-;Feh.  +. 

Cerebral  Thrombosis. — The  hemiplegias  and  paretic  con- 
ditions produced  by  the  gradual  occlusion  of  blood-vessels 
give  us  the  serology  of  the  etiologic  factor  responsible  for 
their  existence.  If  syphilis  is  the  cause,  one  is  apt  to  obtain 
a  positive  Wassermann  reaction  in  the  serum;  here,  as  well 
as  in  other  neurologic  disorders,  a  positive  Wassermann 
reaction  in  the  serum  bears  only  a  secondary  significance 
in  the  serology  of  the  disease.  In  thrombotic  brain  diseases 
one  is  more  often  confronted  with  the  question  of  syphilis 
than  in  the  hemorrhagic  cases.  Nevertheless,  a  positive 
Wassermann  serum  reaction,  in  the  absence  of  findings 
of  a  pathologic  nature  in  the  cerebrospinal  fluid,  need  not 
be  considered  as  final  proof  of  the  syphilitic  nature  of  the 
thrombosis.  Although  suggestive  of  syphilis,  when  the 
test  is  positive  in  the  serum  only,  its  significance  is  greatly 
enhanced  when  the  cerebrospinal  fluid  contains  -either  an 
excess  of  globulin  with  a  pleocytosis,  or  only  the  latter.  In 
such  a  case  the  Wassermann  reaction  may  be  absent  in  the 
cerebrospinal  fluid  without  reducing  the  significance  of  the 
collective  findings.  A  positive  reaction  in  the  fluid  is  at 
times  obtained  in  such  cases,  which,  of  course,  settles  the 
entire  question  of  etiology  and  treatment.  The  increase 
in  cells,  if  present,  is  usually  of  those  of  the  small  mono- 
nuclear variety,  and,  as  a  rule,  it  very  rarely  exceeds  the 
pathologic  increase;  border-line  counts  are  the  rule,  with  a 
normal  globulin  content  and  a  normal  Fehling's  reduction. 
Average  formula:  S.:  W.  R.  -  ;  C.  S.  F.:  W.  R.  -  ;  Gl.  - ; 
PL  — ;  Feh.  +  .  Luetic  average  formula:  S.:  W.  R. +; 
C.  S.  F.:  W.  R.  +  or  -;  GL-  ;  PL  +;  Feh.  +. 

Cerebral  Tumor. — The  serology  of  cerebral  tumors  is  al- 
most negative.  In  the  case  of  gumma  one  may  find  a  posi- 
tive Wassermann  reaction  in  the  cerebrospinal  fluid,  with  a 
border-line  or  a  pathologic  cell  count.  I  have  never  seen  a 
pathologic  increase  or  a  hyperlymphocytic  count.  The  sig- 
nificant serology  of  spinal  cord  tumors  is  not  obtainable 


BRAIN   DISEASES  97 

with  brain  neoplasms,  unless  the  latter  are  situated  in  the 
posterior  fossa  of  the  skull. 

In  estimating  the  value  of  a  positive  Wassermann  reaction 
in  the  serum  of  a  given  case  of  brain  tumor,  one  must  be 
more  cautious  than  in  any  other  neurologic  disorder.  A 
positive  Wassermann  serum  reaction  was  obtained  in  a  case 
of  brain  endothelioma  with  a  coexistent  gumma  of  the  liver. 
Only  unquestionable  spinal  fluid  positive  Wassermann  reac- 
tions should  make  one  accept  syphilis  as  the  cause  of  the 
tumefaction. 

The  question  of  therapy  is  by  no  means  settled  by  a 
positive  Wassermann  reaction  in  the  cerebrospinal  fluid  and 
an  increased  cell  count.  Antisyphilitic  treatment  is  to  be 
resorted  to  only  in  case  the  tumor  is  not  situated  in  the 
neighborhood  of  vital  centers  and  when  its  size  is  small 
enough  to  encourage  the  hope  that  such  treatment  will  effect 
its  disappearance.  In  all  other  tumor  cases  surgery  as  prac- 
tised today  is  a  much  more  rational  and  satisfactory  proce- 
dure than  medical  treatment.  One  must  also  not  be  misled 
by  the  successful  negativation  of  the  serologic  findings  by 
drug  treatment;  it  should  be  borne  in  mind,  especially  in 
cases  of  brain  tumor,  that  the  patient  is  suffering  from  a 
neoplasm,  and  not  from  a  positive  serology.  There  are 
cases  on  record  in  which  the  patient,  regardless  of  the  fact 
that  a  negative  serology  was  obtained  as  the  result  of  drug 
therapy,  succumbed  to  the  tumor,  which  proved  to  be  a 
gumma. 

It  must  be  conceded  that  inaccessible  tumors  of  the  brain 
are  not  helped  by  any  form  of  treatment,  whether  the 
serology  is  positive  or  negative.  As  cases  of  sudden  death 
have  been  recorded  as  a  direct  result  of  the  rachicentesis  in 
cases  of  brain  tumor,  caution  must  be  exercised,  particu- 
larly when  the  tumor  is  located  in  the  posterior  fossa  of  the 
skull.  When  it  is  absolutely  necessary  to  make  the  puncture 
it  is  advisable,  in  order  to  avoid  unpleasant  consequences, 
to  replace  the  removed  fluid  immediately  by  injecting  an 
equal  quantity  of  normal  sterile  saline  solution,  and  to  raise 
the  foot  of  the  bed  about  12  to  15  inches.  It  seems  that  the 
tumor  in  the  posterior  fossa  as  the  result  of  the  removed 

7 


98        SEROLOGY   OF   NERVOUS   AND    MENTAL   DISEASES 

fluid  encroaches  upon  the  vital  center  in  the  floor  of  the  fourth 
ventricle,  causing  respiratory  or  cardiac  inhibition.  The 
reintroduced  saline  solution  may  refill  the  cushion  of  fluid 
and  thus  obviate  fatalities,  and  the  raised  foot  of  the  bed 
will  tend  to  deviate  by  gravity  the  line  of  pressure  away  from 
the  vital  centers.  Average  formula:  S.:  W.  R.  —  or  +; 
C.  S.  F.:  W.  R.  -  or  +;  Gl.  +  or  -;  PL  -;  Feh.  +. 

Cerebral  Abscess. — In  almost  one-third  of  the  cases  of 
cerebral  abscess  the  ear  is  the  starting-point  of  the  purulent 
process.  Rachicentesis  gives  abnormal  findings,  as  a  rule, 
when  the  accumulation  of  pus  gives  rise  also  to  a  meningitic 
reaction.  This,  however,  is  not  an  absolute  requirement, 
as  there  are  instances  in  which  a  pleocytosis  and  an  increase 
in  protein  were  observed  without  a  demonstrable  meningitis. 
A  well-encapsulated  abscess  of  the  cerebrum  will  give  a  nega- 
tive result  in  the  cerebrospinal  fluid,  no  matter  where  it  is 
situated.  When  a  diffuse  purulent  meningitis  is  to  be  differ- 
entiated from  a  cerebral  abscess,  the  performance  of  a  lum- 
bar puncture  may  frequently  be  of  decisive  importance. 
The  former  condition  always  presents  a  turbid  fluid  rich  in 
cells  (meningitic  cell  count),  and  shows  a  protein  excess,  as 
well  as  bacteria.  All  these  pathologic  constituents  are  to  be 
observed  only  when  the  communication  with  the  subarach- 
noid space  is  free;  if  it  is  shut  off,  one  may  find  only  a  few 
cells  (border-line  count),  with  or  without  a  mild  protein  ex- 
cess. It  is  also  important,  in  cases  of  diffuse  purulent 
meningitis,  to  observe  the  behavior  of  the  fluid  toward 
Fehling's  solution.  At  the  height  of  the  meningitis  one  ob- 
tains no  reduction  of  the  solution,  which,  however,  appears 
as  the  acute  stage  gives  place  to  a  chronic  condition.  As 
the  greatest  difficulty  is  often  encountered  in  differentiating 
between  a  diffuse  meningitis  and  an  abscess,  the  points  just 
considered  will  prove  of  great  usefulness.  Average  formula: 
S.:  W.R.-;  C.S.F.-;  Gl.  -  or  +;  PL  +  or-;  Feh. +. 

Cerebral  Softening. — This  condition  may  give  a  positive 
serology  in  those  cases  in  which  lues  is  the  etiologic  factor. 
Where  the  softening  is  due  to  a  simple  arteriosclerosis,  one 
may  occasionally  find  only  a  few  cells  (border-line  count), 
and  rarely  only  a  slight  protein  excess.     In  the  luetic  cases 


BRAIN   DISEASES  99 

the  Wassermann  reaction  in  the  cerebrospinal  fluid  need 
not  be  positive,  even  when  the  "Auswertungs  Methode" 
is  employed.  The  reduction  of  Fehling's  solution  is  always 
obtained.  There  are  instances  in  which,  as  a  result  of  the 
proximity  to  the  meninges,  a  secondary  meningitis  is  pro- 
duced, with  the  usual  serology  in  such  cases.  (See  Menin- 
gitis.) Average  formula :  S. :  W.  R.  - ;  C.  S.  F. :  W.  R.  - ; 
Gl.-;  Pl.-;Feh.  +. 

Hydrocephalus. — In  this  condition  one  usually  finds  a 
normal  cell  count.  The  globulin  is  present  in  normal  quan- 
tities only.  It  is  to  be  conceded  that  occasionally  one 
finds  a  fluid  with  a  border-line  or  a  pathologic  cell  count; 
these  cases  usually  also  give  a  positive  Wassermann  reac- 
tion in  either  the  spinal  fluid  or  serum  or  in  both.  This  applies 
to  the  chronic,  quiescent  cases  of  hydrocephalus.  In  acute 
cases  the  cell  increase  may  be  decided  and  the  globulin  in 
excess.  In  such  instances  the  pressure  of  the  stream  is  an 
important  point  to  be  considered;  Quincke  reports  cases 
in  which  the  pressure  was  over  1000  mm.  The  objective 
symptoms  frequently  improve  after  an  abundant  withdrawal 
of  fluid,  which  procedure  is  to  be  performed  with  caution 
and  with  the  use  of  a  manometer,  not  permitting  the  pres- 
sure to  return  quite  to  the  normal.  In  post-traumatic 
hydrocephalus  (concussion  of  the  brain)  the  cerebrospinal 
fluid  is  usually  increased  in  amount;  the  pressure  is  also 
increased,  while  the  cells  and  the  globulin  content  are,  as  a 
rule,  normal.  In  this  condition  repeated  puncture  and  with- 
drawal of  fluid  is  frequently  followed  by  improvement  in  the 
objective  symptoms. 

According  to  Quincke,  the  headaches  of  chlorotic  indi- 
viduals are  due  to  a  condition  that  he  designates  as  hydro- 
cephalus angioneuroticus.  Average  formula:  S.:  W.  R.  — ; 
C.S.F.:  W.R.-;Gl.-;Pl.-;Feh.  +. 

Amaurotic  Family  Idiocy. — This  disease  belongs  to  the 
large  group  of  hereditary  or  congenital  diseases  more  or  less 
closely  related  to  the  diplegias.  Sachs  believes  that  this 
affection  is  to  be  observed  exclusively  among  the  Jews. 
Properly  classified,  it  ought  not  to  be  considered  with  brain 
diseases,  as,  according  to  Frey,  the  pyramidal  fibers  are 


100      SEROLOGY   OF   NERVOUS    AND    MENTAL    DISEASES 

extensively  atrophied,  besides  degeneration  of  the  cortical 
cells. 

But  little,  if  any,  serologic  work  has  been  done  on  this 
very  interesting  and  obscure  affection.  I  had  the  oppor- 
tunity to  study  the  serology  in  one  patient,  and  could  find  no 
deviation  from  the  normal  in  the  serum  or  in  the  cerebrospinal 
fluid.  In  another  patient,  where  the  serum  only  was  avail- 
able for  study,  and  gave  a  negative  Wassermann  reaction, 
the  parents  were  also  examined,  with  the  result  that  the 
mother  gave  a  positive  and  the  father  a  negative  Wasser- 
mann result.  It  seems  to  me  that  the  positive  reaction 
(syphilis?)  bears  no  etiologic  relationship  to  this  disease. 
Had  the  spinal  fluid  Wassermann  been  positive,  we  would 
have  formed  quite  a  different  conception  of  the  entire 
process.  In  two  other  babies  the  serum  Wassermann  was 
found  to  be  negative.  It  is  to  be  hoped  that  in  the  future 
more  extensive  chemical  studies  of  this  form  of  infantile 
cerebrospinal  degeneration  will  be  made,  especially  on  the 
spinal  fluid.  Average  formula:  S.:  W.  R.  — ;  C.  S.  F.: 
W.  R.-;  Gl.-;  PL-;  Feh.  +. 

SPINAL  CORD  DISEASES 

Spinal  Spastic  Paralysis  (Lateral  Sclerosis). — This  is  a 
well-defined  clinical  entity,  and  in  the  adult,  considered 
from  the  serologic  point  of  view,  is  entirely  negative.  When, 
however,  syphilis  is  present  as  the  etiologic  factor  of  the 
lateral  sclerosis,  or  is  only  a  coexistent  factor,  great  care  is 
required  for  its  proper  interpretation.  In  the  former  one 
would  expect  cerebrospinal  fluid  abnormalities,  with  or 
without  a  positive  Wassermann  reaction  in  the  fluid  or  in 
the  serum  or  in  both  media;  in  the  latter  instance  abnor- 
malities in  the  fluid  should,  of  course,  be  absent.  Average 
formula:  S.:  W.  R.  - ;  C.  S.  F.:  W.  R.-;  GL-;  PL-; 
Feh.  +. 

Congenital  Spastic  Paralysis  (Little's  Disease). — This  is 
preeminently  a  disease  of  the  motor  area.  That  either  the 
brain  or  the  spinal  cord  may  be  implicated  in  the  process 
is  a  possibility;  the  two  are,  however,  usually  found  affected 
together,   and  the  former  more   extensively   so   than   the 


SPINAL   CORD    DISEASES  101 

latter.  The  most  important  etiologic  factor  in  this  condi- 
tion is  cerebral  trauma  inflicted  during  birth,  which  alone  is 
sufficient  to  produce  inhibition  in  the  development  of  the 
pyramidal  tracts.  Only  in  very  few  instances  can  syphilis 
congenitalis  be  considered  as  a  cause  of  the  disease.  The 
serology  of  the  cerebrospinal  fluid  is  usually  negative. 
Not  a  single  case  among  6  analyzed  by  me  gave  a  positive 
serologic  result.  In  one  instance  the  parents  admitted  lues, 
but  gave  a  negative  Wassermann  reaction  in  the  serum.  In 
two  other  instances  the  parents  denied  lues  and  gave  nega- 
tive serum  Wassermann  reactions.  Average  formula:  S.: 
W.  R.  - ;  C.  S.  F.:  W.  R.  -  ;  Gl.  -  ;  PL  - ;  Feh.  +. 

Senile  Spastic  Paraparesis. — As  the  name  implies,  this  is 
a  disease  of  the  aged.  In  the  majority  of  instances  the 
changes  are  similar  to  those  seen  in  arteriosclerosis  of  the 
vascular  system  of  the  spinal  cord,  and  sclerotic  changes 
are  also  seen  near  the  vessels  in  the  white  matter  of  the 
cord.  The  involvement  of  the  cerebral  motor  tracts  by 
small  foci  may  also  give  the  picture  of  a  spastic  paraparesis. 
The  serology  is,  as  a  rule,  negative,  as  lues  can  be  excluded 
in  almost  every  instance.  Average  formula:  S.:  W.  R.  — ; 
C.  S.  F.:  W.  R.  -  ;  Gl.  - ;  PI.  -  ;  Feh.  +.1 

Combined  Sclerosis. — A  few  such  cases  were  observed 
at  the  Neurological  Institute.  All  these  showed  more  or 
less  severe  blood  changes,  although  not  one  assumed  the 
severity,  so  far  as  the  morphology  and  numeric  relation- 
ship are  concerned,  of  the  blood-picture  of  the  so-called 
pernicious  anemia.  The  changes  were  mostly  confined  to 
the  red  blood-corpuscles,  which  showed  granular  and  hemo- 
globinemic  degenerations,  with  or  without  a  polychromato- 
philia.  In  one  case  a  pronounced  anisocytosis,  and  in  an- 
other a  marked  macrocytosis,  were  the  only  abnormalities 
noted.  The  etiology  in  these  cases  was  not  determinable, 
although  it  was  believed  at  one  time  that  some  toxic  sub- 
stance played  the  chief  role.  The  serology  of  these  patients 
was  very  interesting,  in  that  three  of  them  gave  a  marked 
increase  in  the  globulin  content  of  the  cerebrospinal  fluid, 

1  See  Collins  and  Zabriskie,  Medical  Record,  1904;  also  B.  Sachs, 
Revue  of  Neurol.,  1905. 


102      SEROLOGY    OF   NERVOUS   AND   MENTAL   DISEASES 

without  an  increase  in  the  cell  count;  one  gave  a  border-line 
pleocytosis.  Syphilis  could  be  excluded  clinically,  and  if 
the  negative  Wassermann  reactions  can  be  taken  as  sig- 
nificant in  these  instances,  also  serologically.  In  these  cases 
the  globulin  excess  was  so  great  that  even  a  1 :  10  dilution 
gave  the  reaction  usually  obtained  with  an  excess.  It  will 
be  shown  further  on  that  such  findings  are  usually  asso- 
ciated with  a  spinal  cord  compression.1  Average  formula: 
S. :  W.  R.  - ;  C.  S.  F. :  W.  R.  - ;  Gl.  +  or  - ;  PI.  - ;  Feh.  +  . 

Hereditary  Ataxia  (Friedreich's  Disease). — So  far  as  I 
know,  there  are  no  serologic  records  in  the  literature  con- 
cerning the  serology  of  this  rare  neurologic  condition.  One 
case  analyzed  by  me  gave  absolutely  negative  findings. 
It  may,  however,  be  necessary  at  times  to  differentiate 
between  this  affection  and  cerebrospinal  syphilis,  a  task  which 
should  not  offer  any  difficulty  in  view  of  the  serology  of  the 
latter  disease.  I  believe  that  syphilis  is  rarely  a  cause  of  this 
disease.  As  its  name  suggests,  heredity  plays  a  more  im- 
portant part  than  anything  else  in  the  etiology  of  this  nervous 
disorder.  Average  formula:  S.:  W.  R.  — ;  C.  S.  F.:  W.  R. 
-;  Gl.-;  PI.-;  Feh.  +. 

Acute  Myelitis. — In  a  case  where  the  symptoms  were 
ushered  in  somewhat  suddenly,  with  pain  in  the  region  of  the 
spleen  and  the  signs  of  a  transverse  myelitis,  which  was  for 
a  short  time  regarded  as  a  cord  tumor,  severe  degenerative 
blood-changes  were  observed  by  me,  and  the  observations 
reported  together  with  those  of  Dr.  Collins.  The  blood- 
picture  was  described  as  a  promyelocytic  leukemia.  The 
blood-culture  was  negative  (sterile).  During  his  sojourn 
in  the  hospital  the  patient  developed  signs  of  pulmonary  in- 
farction, and  died  a  few  days  later.  The  serology  was  nega- 
tive, with  the  exception  of  a  border-line  count  and  a  slight 
globulin  excess.  In  post-infectious  myelitis  one  usually 
finds  such  changes  in  the  serology,  with  occasional  red  blood- 
corpuscles  and  blood-pigment  in  the  cerebrospinal  fluid. 
The  Wassermann  reaction  is  negative. 

The  reduction  of  Fehling's  solution  may  be  impaired 
and  give  a  violet  tinge  to  the  fluid,  and  only  a  sparse  de- 
1  Dana:.  Jour.  Nerv.  Dis.,  1899. 


SPINAL    CORD   DISEASES  103 

posit  of  reduced  copper  will  be  seen  on  the  bottom  of  the 
test-tube. 

It  cannot  be  denied  that  severe  changes  in  the  blood  may 
exert  deleterious  influences  on  the  cerebrospinal  apparatus, 
and  that  the  abnormal  serology  of  these  patients  is  to  be 
considered  as  of  the  same  significance  as  severe  infections, 
which,  as  is  known,  frequently  render  the  serologic  findings 
abnormal.  The  qualitative  study  of  the  blood  in  these  in- 
stances is  a  very  essential  feature  of  the  entire  clinical  pic- 
ture, particularly  where  the  condition,  in  its  clinical  and 
serologic  aspects,  resembles  a  tumor.  Average  formula: 
S.:W.R.-;  C.  S.  F.:  W.  R.  -;  Gl.  +  or-;  PI.  -  or  +  ?; 
Feh.  +. 

Anterior  Poliomyelitis. — In  the  acute  form  one  usually 
finds  border-line  counts  and  a  normal  or  slightly  increased 
globulin  content.  The  Wassermann  is  usually  negative 
in  the  serum  and  spinal  fluid.  That  positive  Wassermann 
reactions  may  be  obtained  in  the  serum  must  be  admitted; 
a  similar  result  on  the  cerebrospinal  fluid,  however,  should 
make  one  reconsider  both  factors,  clinical  and  serologic, 
for  when  the  Wassermann  reaction  is  truly  positive,  I  would 
not  hesitate  to  doubt  the  clinical  interpretation  of  the  affec- 
tion; on  the  other  hand,  if  repeated  serologic  reports  from 
different  laboratories  do  not  strictly  coincide,  then  the 
serology  should  be  discarded  and  poliomyelitis  accepted  as 
the  clinical  diagnosis.  The  positive  Wassermann  reaction 
obtained  on  the  serum  can  be  accounted  for  by  a  preexisting 
congenital  lues,  but  I  am  inclined  to  consider  the  serologic 
result  as  an  error  in  the  performance  of  the  test,  unless 
distinct  signs  of  congenital  lues  are  at  hand.  As  the  dis- 
ease progresses  and  enters  upon  the  prolonged  chronic  stage, 
one  usually  finds  nothing  abnormal  in  the  serology  with 
the  exception  of  a  positive  Wassermann  reaction  in  the 
serum  in  congenital  syphilitics.  There  are  no  definite  land- 
marks in  the  serology  of  poliomyelitis,  nor  does  bacteriology 
help  us  in  this  instance,  although  a  filterable  toxic  substance 
was  obtained  which  proved  to  be  noxious  to  monkeys. 
Average  formula:  S. :  W.  R.  - ;  C.  S.  F. :  W.  R.  - ;  Gl.  -  ; 
PL-;  Feh.  +. 


104      SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

A  very  important  contribution  to  our  knowledge  of  this 
affection  was  given  by  Peabody,  Draper,  and  Dochez.  These 
observers  find  a  variably  high  pressure,  which,  however,  is 
not  diagnostic.  The  cells  are  exceedingly  numerous  in  the 
earliest  stages  of  the  disease,  at  which  time  the  percentage 
of  polynuclear  elements  may  exceed  75  per  cent.  As  the 
disease  progresses  the  number  of  cells  tends  to  diminish 
and  may  reach  the  normal  or,  at  most,  border-line  counts. 
They  find  the  highest  counts  in  the  preparalytic  stage  of  the 
disease,  the  number  of  cells  gradually  diminishing  to  normal. 
Of  45  cases,  8  showed  50  cells  and  over  per  c.mm.,  while 
in  the  second  week  23  gave  normal  counts.  Of  40  cases 
in  the  third  week,  only  one  gave  a  count  of  over  50,  while 
only  8  were  above  normal.  As  compared  with  the  cell  count, 
the  globulin  content  is,  as  a  rule,  low  in  the  first  part  of  the 
acute  stage,  tends  to  rise  during  the  second  and  third  weeks 
of  the  disease,  and  then  gradually  falls.  These  authors  con- 
clude that  the  marked  cellular  increase  is  characteristic  of 
the  early  stage  of  the  disease,  and  that  the  higher  globulin 
contents  are  significant  of  the  more  or  less  advanced  form. 
The  foregoing  studies  were  conducted  on  children,  but  it  must 
not  be  forgotten  that  acute  anterior  poliomyelitis  was  also 
observed  in  the  adult,  although  no  rachicentesis  was  per- 
formed. The  danger  in  such  instances  is  the  suspicion  of 
syphilis,  which  may  defer  proper  treatment  in  due  time. 

Amyotrophic  Lateral  Sclerosis. — In  this  very  interesting 
disease  the  serology  is,  as  a  rule,  entirely  negative.  Al- 
though I  had  the  opportunity  of  analyzing  only  6  cases,  I 
believe  I  am  justified  in  making  this  statement,  in  view  of  the 
absence,  in  the  literature,  of  anything  to  the  contrary. 
Again,  a  positive  Wassermann  can  be  obtained  in  the  serum 
of  those  who  were  infected  subsequently  to  the  development 
of  the  amyotrophic  condition.  It  is  an  accepted  fact  that 
syphilis  as  an  etiologic  factor  has  no  bearing  on  this  affec- 
tion, although  it  must  be  admitted  that  a  lesion  of  the 
anterior  horn  cells  and  the  pyramidal  tracts  can  be  pro- 
duced by  syphilis.  Average  formula:  S.:  W.  R.  — ;  C.  S. 
R:  W.R.-;  Gl.-;  PL-;  Feh.  +. 

Progressive  Muscular  Atrophy  (Spinal  Form). — In  this 


SPINAL  CORD  DISEASES  105 

disease,  but  in  a  few  instances  only,  syphilis  plays  an  etio- 
logic  role.  This  contention  was  advanced  by  Dana1  in  his 
statistics.  In  one  patient  only  was  I  able  to  obtain  a  posi- 
tive Wassermann  reaction  in  the  serum,  the  history  of 
syphilis  antedating  the  advent  of  the  neurologic  disorder. 
In  another  patient  who  gave  a  suspicious  history  a  nega- 
tive Wassermann  was  obtained  on  the  serum,  but  another 
reaction,  which  will  be  spoken  of  further  on,  was  positive. 
The  cerebrospinal  fluid  was  negative  in  5  cases  observed  by 
me.  I  cannot  state  whether  remedies  directed  against 
syphilis  arrested  the  progress  of  this  disease.  Average  for- 
mula: S.:  W.  R.-  or  +;  C.  S.  F.:  W.  R.-;  Gl.-; 
PL-;  Feh.  +. 

Progressive  Muscular  Atrophy. — In  typical  cases  this  dis- 
ease shows  no  appreciable  changes  in  the  cord  or  nerves; 
the  muscles  are  the  seat  of  the  pathologic  process.  The 
serology  is  entirely  negative.  Average  formula:  S.:  W.  R. 
-;  C.S.F.:  W.R.-;  Gl.-;  PI.-;  Feh.  +  . 

Progressive  Muscular  Atrophy  (Neurospinal  Form). — 
Although  heredity  plays  an  important  etiologic  role  in  this 
disease,  syphilis  is  not  considered  as  a  factor.  In  two  in- 
stances the  serology  was  negative.  The  possibility  of 
subsequent  contamination  with  syphilis  after  the  advent  of 
the  neurologic  disorder  must  always  be  borne  in  mind.  (See 
the  section  on  General  Considerations.) 

In  such  an  instance  a  positive  Wassermann  reaction  de- 
mands great  care  in  establishing  the  time  relationship  be- 
tween the  infection  and  the  beginning  of  the  neurologic  dis- 
order. In  such  cases  also  the  Wassermann  test  should  be 
performed  more  than  once,  and  preferably  by  different  se- 
rologists.  Average  formula:  S. :  W.  R.  — ;  C.  S.  F. :  W.  R.  —  ; 
Gl.-;  PI.-;  Feh.  +. 

Multiple  Sclerosis. — This  disease  is  not  nearly  so  prevalent 
in  America  as  it  is  in  Europe.  I  had  the  opportunity  of  ana- 
lyzing 16  cases  serologically.  In  only  3  was  the  Wassermann 
reaction  positive  in  the  serum,  all  having  shown  anamnesic 
factors  of  lues.  Not  one  case  gave  a  positive  Wassermann 
reaction  in  the  cerebrospinal  fluid,  the  original  Wassermann 
1  Dana:   Jour,  of  Nerv.  Dis.,  1906. 


106      SEROLOGY   OF   NERVOUS    AND    MENTAL   DISEASES 

method  being  used.  The  cells  were  always  within  the 
normal  limits  or,  at  most,  gave  the  smaller  of  the  border-line 
count.  The  globulin  was  never  found  to  be  in  excess,  and 
the  Fehling  reduction  was  prompt.  It  is  my  opinion,  al- 
though supported  by  only  16  analyses,  that  it  is  safer  to 
regard  the  finding  of  a  positive  Wassermann  in  the  cerebro- 
spinal fluid  in  this  disease  as  a  technical  error  than  to  assume 
that  syphilis  is  the  cause  in  a  given  case  of  multiple  sclerosis. 
The  obtaining  of  a  positive  result  with  the  "Auswertungs 
Methode"  is,  in  my  opinion,  of  value  only  when  the  same  is 
obtainable  with  the  use  of  smaller  amounts  of  fluid — as 
little  as  0.1  c.c.  The  absence  of  a  pleocytosis  and  of  a 
globulin  excess  greatly  minimizes  the  genuineness  of  a  posi- 
tive Wassermann  reaction  obtained  in  the  cerebrospinal 
fluid  in  this  disease.  Concerning  this,  more  will  be  said 
further  on.1  Average  formula:  S.:  W.  R.  — ;  C.  S.  F.: 
W.R.-;  Gl.-;  PL-;  Feh. +. 

Syringomyelia. — In  this  condition  one  may  obtain  a 
marked  increase  of  protein  without  a  pleocytosis.  As  a 
rule,  the  Wassermann  reaction  is  negative,  as  it  has  nothing 
in  common  with  this  disease.  In  one  instance  the  fluid 
was  colored  a  lemon  yellow  and  did  not  give  a  Berlin-blue 
reaction.  In  four  other  cases  the  fluid  was  absolutely 
normal.  Average  formula:  S.:  W.  R.  — ;  C.  S.  F. :  W.  R. 
-;  Gl.-  or  +;  PI.-;  Feh.-. 

Hematomyelia. — A  hemorrhage  may  take  place  in  a  pre- 
existing cavity  as  the  result  of  a  syringomyelia.  The  con- 
dition is  not  a  very  common  one,  and  is  usually  observed  in 
those  whose  health  is  below  par,  and  whose  spinal  cord  is 
less  resistant  than  normally.  Whether  syphilis  can  so  alter 
the  nutritive  balance  of  the  cord  tissues  as  to  make  them  less 
resistant  to  sudden  or  prolonged  strain  and  thus  induce 
rupture  of  a  blood-vessel  is  not  known.  In  two  instances — 
one  a  girl  of  seventeen  and  another  a  man  of  forty-two — 
no  abnormalities  were  observed  in  the  fluid  or  the  serum. 
The  patients  were  studied  a  few  months  after  the  acute 
attack.  What  the  serology  would  have  shown  had  the  fluid 
been  analyzed  immediately  after  the  hemorrhage  is  merely 
1  See  Kaplan:  Deut.  med.  Woch.,  May  29,  1913. 


SPINAL   CORD    DISEASES  107 

presumptive.  Average  formula:  S.:  W.  R.  — ;  C.  S.  F.: 
W.R.-;  Gl.-;  PI.-;  Feh.  +. 

Spondylitis  Tuberculosa. — The  serology  of  this  condition 
depends  entirely  upon  the  extent  of  the  involvement  of  the 
contents  of  the  vertebral  canal.  A  small  tuberculous  focus 
that  does  not  interfere  with  the  integrity  of  the  meninges 
will,  as  a  rule,  give  rise  to  no  abnormalities  in  the  cerebro- 
spinal fluid;  on  the  other  hand,  if  great  swelling  and  cord 
compression  is  produced,  the  fluid  will  be  altered  and  will 
show  an  excess  of  protein  matter  (globulin?)  and  also  a  few 
cells.  Not  until  a  meningitis  is  produced  will  the  fluid  show 
a  pathologic  or  a  hyperlymphocytic  count.  In  one  case, 
described  under  the  head  of  Hypertrophic  Laminated  Spinal 
Pachymeningitis,  the  etiologic  factor  was  most  likely  a  tuber- 
culous focus  in  the  vertebra?,  and  the  laminated  structure 
in  that  case  could  be  regarded  as  a  means  of  protection 
against  invasion  by  the  tubercle  bacillus.  Average  formula : 
S.:  W.  R.-;  C.  S.  F.:  W.  R.-;  Gl.  +  or-;  PI.-; 
Feh.  +. 

Tumors  of  the  Spinal  Cord. — Strictly  speaking,  any  factor 
that  is  capable  of  exerting  pressure  on  the  cord  shows  the 
serology  commonly  encountered  in  tumors.  New-formations 
in  this  region  may  be  either  extradural,  intradural,  or  intra- 
medullary. If  the  tumor  is  large  enough  to  produce  com- 
plete occlusion  of  the  spinal  sac  below,  the  cerebrospinal 
fluid  will  be  very  scanty  and  at  times  no  fluid  at  all  will  be 
obtainable. 

Intradural  and  extramedullary  tumors,  as  well  as  extra- 
dural new-formations,  give  rise  to  a  paradoxic  reaction 
in  the  cerebrospinal  fluid;  in  70  per  cent,  of  cases  analyzed 
by  me  a  great  excess  of  protein  matter  was  obtainable.  The 
reaction  was  so  marked  that  a  1 : 5  and  even  greater  dilu- 
tion gave  excessive  response.  Regardless  of  the  great  protein 
excess,  a  pleocytosis  was  but  rarely  encountered,  and  never 
exceeded  the  border-line  count.  In  one  case  of  gumma  of  the 
dorsal  cord  the  cerebrospinal  fluid  likewise  gave  a  posi- 
tive Wassermann  reaction.  This  patient  showed  14  cells 
per  c.mm. 

Of  the  31   fluids  analyzed,  8  showed  a  xanthochromia 


108      SEROLOGY   OF   NERVOUS    AND   MENTAL    DISEASES 

(citron-yellow  color);  6  of  these  proved  to  be  endothelio- 
mata,  and  the  yellow  color  of  the  other  two  was  probably 
due  to  hemorrhages  in  tumors  with  cystic  degenerations. 
It  is  possible,  too,  that  the  needle  used  in  making  the 
lumbar  puncture  may  have  entered  one  of  these  cysts. 

In  one  of  these  two  cases  a  few  cells  were  observed  that 
carried  blood-pigment,  as  determined  by  the  iron  reaction; 
a  similar  result  was  obtained  with  the  cerebrospinal  fluid. 
The  operation  in  this  case  revealed  an  intramedullary 
growth,  with  abundant  hemorrhages,  and  cells  that  con- 
tained the  same  iron-reacting  substance  as  was  obtained 
by  the  puncture. 

In  one  case  of  cord  tumor  with  yellow  fluid  the  liquid  con- 
gealed in  the  test-tube  and  had  the  appearance  of  a  thin 
pellicle  which  could  be  removed  without  destroying  its 
contour.  Of  the  above  8  cases  with  yellow  fluid,  2  showed  no 
reduction  of  Fehling's  solution.  The  reaction  of  a  protein 
excess  without  a  pleocytosis  is  very  characteristic  of  cord 
compression.  The  same  serologic  findings  were,  however, 
obtained  in  other  diseases.  (See  Combined  Sclerosis,  Dis- 
ease of  the  Cauda  Equina,  Syringomyelia,  Spondylitis 
Tuberculosa.)  The  two  last-named  conditions  may  be 
regarded  as  productive  of  mechanical  cord  compression. 

The  question  of  treatment  depends  greatly  upon  the 
etiology  of  the  new-growth;  if  the  globulin  excess  is  ac- 
companied by  a  pathologic  cell  count  and  a  positive  Wasser- 
mann,  as  well  as  by  a  history  of  specific  infection,  the  patient 
is  to  be  given  a  course  of  antiluetic  treatment.  Where  the 
diagnosis  of  an  extramedullary  growth  is  fairly  certain 
and  the  subjective  symptoms  are  very  distressing,  it  is 
perhaps  advisable  to  proceed  surgically  at  once,  and  take 
up  the  treatment  with  specifics  later. 

It  is  a  very  dangerous  procedure  to  attempt  to  remove 
tumors  situated  in  the  upper  cervical  or  lower  medullary 
region.  The  resulting  edema  and  congestion,  and  at  times 
post-operative  hemorrhage,  are  fatal.  Nevertheless,  I  know 
of  at  least  three  patients  in  whom  an  operation  was  per- 
formed in  this  region;  in  one  of  these  an  intramedullary 
growth  was  removed  and  the  patient  is  -doing  well  after  three 


NERVE    AFFECTIONS  109 

years.  Average  formula:  S.:  W.  R.  —  ;  C.  S.  F.:  W.  R.  — ; 
Gl.  ++  or  -  ;  PL  - ;  Feh.  +  or  -. 

Disease  of  the  Cauda  Equina. — The  cauda,  being  subject 
to  the  same  diseases  as  the  upper  cord,  will  also  show  the 
same  serology.  In  two  instances  in  which  the  diagnosis  of 
tumor  was  made  and  no  growth  was  found  at  operation,  the 
cerebrospinal  fluid  gave  the  reaction  of  a  protein  excess. 
The  examination  of  the  cauda  showed  a  mild  form  of  neu- 
ritis of  the  roots.  No  cells  were  found  in  the  fluid.  Average 
formula:  S.:  W.  R.-;  C.  S.  F.:  W.  R.-;  Gl.  +  or-; 
PL-;  Feh.  +. 

Tumors  of  the  Spinal  Column. — Unless  the  contents  of 
the  vertebral  canal  are  encroached  upon,  the  serologic  find- 
ings will  be  normal.  Metastatic  foci  may  produce  sufficient 
irritation  to  produce  the  serology  of  a  meningitis.  It  is 
sometimes  possible  to  detect  the  nature  of  the  malady  by  dis- 
covering atypical  cells,  which,  together  with  other  sug- 
gestive signs,  should  make  one  apprehensive  of  a  metastatic 
process.  The  pressure  of  a  growth  of  the  bodies  of  the 
vertebrae  may  or  may  not  give  an  excess  of  protein.  If  this  is 
present,  however,  it  favors  the  diagnosis  of  such  a  metas- 
tasis. Average  formula:  S. :  W.  R.  - ;  C.  S.  F. :  W.  R.  - ; 
Gl.-;  PL-;  Feh.  +. 

NERVE  AFFECTIONS 

Multiple  Neuritis. — Alcoholic. — In  this  form  of  neuritis 
the  findings  are  at  times  so  suggestive  of  locomotor  ataxia 
that  the  term  "pseudotabes  alcoholica"  seems  to  be  justi- 
fiable in  such  cases.  Even  with  extraordinary  precautions  it 
is  sometimes  very  difficult  to  differentiate  between  this  dis- 
ease and  neuritis  alcoholica  multiplex.  It  is  needless  to 
state  that  the  typical  cases  are  not  included  in  this  dis- 
cussion. 

In  my  laboratory  it  was  not  infrequently  my  task  to  de- 
cide for  or  against  the  existence  of  tabes,  and  sometimes  even 
to  take  a  stand  against  the  diagnosis  of  the  latter  disease. 
I  remember  a  case  in  which  the  history  given  by  the  patient 
was  highly  suggestive  of  lues,  and  the  patient  was,  besides, 
decidedly  alcoholic.    The  serology  was  entirely  negative,  and 


110      SEROLOGY  OF   NERVOUS   AND   MENTAL   DISEASES 

a  more  complete  analysis  of  the  case  proved  the  correct- 
ness of  my  contention.  Such  occurrences  are  not  common, 
but  they  are,  nevertheless,  liable  to  arise  in  any  well-equipped 
hospital.  In  this  connection  one  must  be  particularly  cau- 
tious not  to  consider  a  case  presentation  complete  until  a 
serologic  report  has  been  received,  especially  when  the  pa- 
tient, in  addition  to  his  polyneuritic  symptoms,  shows  also  a 
mental  disorder,  as  is  the  case  with  the  Korsakow  symptom- 
complex.  A  negative  serology  in  such  a  patient  is  strongly 
suggestive  of  a  non-luetic  disease.  In  the  latter  disease, 
however,  one  may  occasionally  encounter  a  border-line  cell 
count,  and  with  it  also  a  slight  excess  of  globulin;  more 
often  the  serology  is  negative. 

The  serology  depends  entirely  upon  the  distribution  of  the 
pathologic  process;  it  is  by  no  means  settled  that  the  neuri- 
tides  are  affections  confined  to  the  peripheral  nerves;  it  is  not 
an  unusual  occurrence  to  find,  with  the  pathology  of  the 
peripheral  nerves,  an  ascending  process  in  the  ganglia,  roots, 
and  tracts  which  may  be  responsible  for  the  abnormalities 
encountered  in  the  cerebrospinal  fluid.  The  importance  of 
a  positive  Wassermann  in  this  connection  is  self-evident, 
particularly  if  obtained  on  the  spinal  fluid;  if  obtained  on 
the  serum,  its  value  is  questionable. 

I  do  not  wish  to  convey  the  impression  that  the  laboratory 
possesses  a  means  of  excluding  tabes,  even  if  the  picture  is 
not  classic  for  this  disease.  It  must  be  remembered  that  in 
tabes  one  may  find  a  negative  serology,  as  will  be  shown  later, 
and  to  exclude  this  disease  on  the  evidence  of  a  serologic 
report  is  certainly  not  advisable.  Although  the  difficulties 
are  many,  it  is  an  extremely  rare  coincidence  to  find  a  patient 
who  presents  doubtful  symptoms  of  locomotor  ataxia,  denies 
syphilis,  admits  alcoholism,  and  presents  a  negative  serology 
without  having  been  previously  treated.  In  view  of  the 
facts  presented  above,  it  is,  in  my  opinion,  safe  to  exclude 
tabes,  and  search  for  other  signs  suggestive  of  some  clinical 
entity  other  than  locomotor  ataxia.  Average  formula: 
S.:  W.R.-;  C.S.F.:  W.R.-;  Gl.-;  Pl.-;Feh. +. 

Lead  Neuritis. — In  this  disease  the  serology  is  absolutely 
normal,  at  least  so  far  as  I  was  able  to  ascertain.    The  mor- 


MISCELLANEOUS    AFFECTIONS  111 

phologic  study  of  the  red  blood-corpuscles  is  a  very  useful 
guide  in  confirming  the  history  and  the  clinical  findings. 
Average  formula:  S.:  W.  R.-;  C.S.F.:  W.R.-;  GL-; 
PL-  Feh.  +. 

Diphtheric  Neuritis. — In  two  cases  the  cerebrospinal 
fluid  showed  no  changes  from  the  normal.  The  blood  was 
negative  to  the  Wassermann  test;  in  one  case  the  father 
of  the  patient  had  an  infection. 

Several  workers  found  that  the  spinal  fluid  of  some  patients 
with  a  post-diphtheric  neuritis  showed  a  border-line  count  and 
an  excess  of  globulin,  and  that  this  would  disappear  as  the 
neuritic  process  subsided.  Average  formula:  S.:  W.R.  —  ; 
C.  S.  F.:  W.  R.  - ;  Gl.  -;  PL --;  Feh.  +. 

Diabetic  Neuritis. — The  spinal  fluid  occasionally  shows 
an  excess  of  glucose.  Acetone  may  also  be  determined  by 
the  iodoform  test.  Some  authors  claim  to  have  obtained 
diacetic  and  even  oxybutyric  acid  reactions.  In  the  terminal 
stages  of  the  diabetic  process  it  is  possible  to  obtain  all  sub- 
stances resulting  from  an  insufficient  catabolism  of  carbo- 
hydrates. Average  formula:  S. :  W.  R.  — ;  C.  S.  F. : 
W.R.-;  GL— ;  PI.  -  Feh. +. 

Herpes  Zoster. — The  herpes  occurring  occasionally  during 
salvarsan  administration  will  not  be  considered  here.  The 
various  forms  of  zoster  having  a  posterior  ganglionitis  as 
their  pathologic  basis  show  an  increase  of  cells  in  the  spinal 
fluid.  In  those  cases  where  a  cell  count  of  over  30  cells 
per  c.mm.  is  obtainable  the  fluid  may  also  give  the  reaction 
of  a  globulin  excess.  Fehling's  solution  is  always  reduced. 
The  pleocytosis  in  this  disease  will  frequently  remain  some 
time  after  the  clinical  signs  have  disappeared.  Average 
formula:  S.:  W.  R.  -;  C.  S.  F.:  W.  R.  -;  Gl.  -;  PL  +  or 
-;  Feh.  +. 

MISCELLANEOUS  AFFECTIONS 

Functional  Nervous  Disorders 

Hysteria. — Hysteric  attacks  occurring  in  a  patient  who 
has  come  in  contact  with  syphilis  will,  of  course,  give  a 
positive  Wassermann  reaction  in  the  serum,  depending  upon 


112      SEROLOGY  OF  NERVOUS    AND   MENTAL   DISEASES 

the  length  of  time  that  has  elapsed  since  the  last  antiluetic 
treatment.  The  cerebrospinal  fluid  is  entirely  normal,  even 
in  those  who  suffer  from  a  coincident  systemic  lues.  After 
a  severe  attack  the  pressure  is  frequently  increased.  Average 
formula:  S. :  W.  R.  -  ;  C.  S.  F. :  W.  R.  - ;  Gl.  - ;  PI.  - ; 
Feh.  +. 

Neurasthenia. — Some  laboratory  workers  accept  without 
question  a  positive  Wassermann  report  on  a  cerebrospinal 
fluid  that  shows  no  other  abnormalities.  If  the  patient  is 
suffering  with  a  severe  neurasthenia,  he  is  unnecessarily 
doomed  to  years  of  treatment  that,  besides  being  unpleas- 
ant, may  tend  to  aggravate  his  nervous  condition.  When, 
pending  the  report  from  the  laboratory,  the  clinician  has 
made  a  tentative  diagnosis  of  severe  neurasthenia,  and  the 
report  of  a  positive  Wassermann  reaction  on  the  cerebro- 
spinal fluid  is  received,  all  doubt  in  the  clinician's  mind  is 
dispelled  and  the  patient  is  treated  as  is  any  other  sufferer 
with  neurologic  syphilis.  This  state  of  affairs  is  still  more 
aggravated  if  the  patient  had  the  misfortune  to  contract 
syphilis  in  addition  to  developing  neurasthenia.  The  ad- 
mission of  an  infection,  together  with  the  clinical  signs  and 
a  positive  Wassermann  on  the  cerebrospinal  fluid,  although 
faulty,  is  sufficient  to  bias  the  diagnostic  opinion  of  even  the 
best  physician.  The  possibility  of  an  infection  with  syphilis 
in  a  true  neurasthenic  must  be  admitted;  this,  of  course, 
could  make  his  serum  react  in  a  positive  manner  to  the 
Wassermann  test,  but  it  could  never  affect  his  cerebrospinal 
fluid  so  as  to  make  it  resemble  the  typical  serology  of  a  general 
paresis  or  cerebrospinal  syphilis.  It  is  well  to  emphasize 
again  the  fact  that  the  laboratory  should  make  it  a  rule  not 
to  report  too  many  positives,  or,  as  was  pointed  out  in  a 
previous  section  on  the  Attitude  of  the  Serologist,  the  error 
committed  in  reporting  a  syphilitic  as  having  a  negative 
Wassermann  in  the  serum  is  of  much  less  consequence 
than  to  return  a  positive  report  on  a  patient  who  has  never 
come  in  contact  with  lues.  To  report  a  positive  Wassermann 
on  a  cerebrospinal  fluid  from  a  patient  free  from  lues  is  in- 
excusable, more  especially  if  the  fluid  shows  no  other  ab- 
normalities, such  as  an  excess  of  globulin  and  a  pleocytosis. 


MISCELLANEOUS   AFFECTIONS  113 

Average  formula:  S. :  W.  R.  -  ;  C.  S.  F. :  W.  R.  -  ;  Gl.  -  ; 
PL-;  Feh.  +. 

Psychasthenia. — The  spinal  fluid  and  serum  show  no 
deviation  from  the  normal. 

Psychoneuroses  (Anxiety,  Compulsion). — In  one  case  of 
compulsion  neurosis  an  increased  pressure  was  observed. 
The  serum  reaction  and  the  other  cerebrospinal  fluid  reac- 
tions were  normal.  Syphilitic  patients  will  give  a  positive 
serum  Wassermann.  Average  formula:  S.:  W.  R.  — ; 
C.  S.  F.:  W.  R.  - ;  Gl.  -  ;  PL  - ;  Feh.  +. 

Spasmophilic  States 

The  Epilepsies. — The  field  of  idiopathic  epilepsies  is  being 
gradually  narrowed  down  to  a  small  number  of  cases  in 
which  no  changes  in  the  central  nervous  system  could  be 
demonstrated  postmortem.  The  development  of  our  knowl- 
edge of  internal  secretory  disorders  makes  it  possible  for  us 
to  treat  some  clinical  manifestations  that  resemble  to  a 
marked  degree  the  symptoms  of  the  genuine  disease,  without 
exhibiting  morphologic  changes  in  the  brain.  In  these  so- 
called  idiopathic  epilepsies  one  or  the  other  of  the  glandular 
extracts,  as  the  case  may  be,  will  influence  the  convulsions 
in  a  way  that  will  ultimately  establish  a  definite  opotherapy 
for  these  conditions,  and  the  designation  of  "idiopathic" 
will  sooner  or  later  be  discarded  in  these  cases.  I  do  not, 
therefore,  speak  of  the  disease  in  the  singular  number,  but 
in  the  plural,  being  convinced  that  there  are  spasmophilic 
states  that  resemble  very  closely  genuine  epilepsy  having 
pathologic  changes  in  the  brain,  and  that  whereas  treat- 
ment with  organic  extracts  proved  of  great  benefit  in  some 
of  these  cases,  I  believe  they  are  caused  primarily  or  in- 
directly by  a  disturbed  equilibrium  (oversecretion,  under- 
secretion,  or  perverted  secretion)  in  one  or  more  of  the 
glands  having  an  internal  secretion. 

Serologically,  there  is  very  little  of  great  moment  in  con- 
nection with  the  epilepsies.  Recent  studies  of  this  disease 
tend  to  lay  great  weight  on  the  significance  of  the  increased 
pressure  of  the  cerebrospinal  fluid.  This  increase  of  pressure, 
however,  is  to  be  obtained  after  any  great  muscular  exertion, 

8 


114      SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

and  particularly  after  convulsions.  In  genuine  epilepsy  one 
rarely  finds  an  abnormal  cerebrospinal  fluid,  although  the 
presence  of  albumin,  a  globulin  excess,  and  a  border-line 
count  were  reported.  In  my  experience,  4  out  of  38  sera  from 
epileptics  gave  a  positive  serum  Wassermann  reaction.  The 
Wassermann  reaction  on  the  cerebrospinal  fluid  was  nega- 
tive in  every  instance,  the  original  Wassermann  method 
being  used.  In  one  case  with  a  positive  Wassermann  reac- 
tion in  the  serum  the  cerebrospinal  fluid  also  showed  23 
lymphocytes  per  c.mm.  The  etiologic  factor  in  this  instance 
was  most  likely  syphilis.  In  another  case  with  a  positive 
Wassermann  the  symptoms  disappeared  entirely  after  anti- 
luetic  treatment;  the  positive  Wassermann,  however,  re- 
mained unchanged.  The  reaction  was  performed  three 
times  with  the  same  result.  In  one  instance  the  positive 
Wassermann  was  most  likely  an  error.  That  syphilis  plays 
an  important  role  in  some  epileptics  must  be  conceded,  one 
of  the  cases  just  described  being  most  likely  an  instance  of 
epilepsy  on  a  syphilitic  basis.  Average  formula:  S.:  W. 
R.-;  C.  S.  R:  W.  R.  - ;  GL-;  PL-  Feh.  +. 

Chorea. — The  various  choreas  of  childhood  or  of  adult  life 
present  little  of  interest  serologically.  Average  formula: 
S.:  W.  R.-;  C.  S.  R:  W.  R.  - ;  Gl.  - ;  PL-;  Feh. +. 

Paralysis  Agitans. — Some  authors  have  found  an  excess 
of  protein  in  the  spinal  fluid.  In  a  number  of  typical  cases 
of  Parkinson's  disease  no  abnormalities  could  be  detected. 
The  calcium  metabolism  of  one  patient  showed  no  deviation 
from  the  normal,  and  the  spinal  fluid  was  normal  in  every 
respect.  In  one  patient  a  positive  Wassermann  on  the 
serum  was  obtained  on  two  occasions.  In  another  patient 
the  mineral  chemistry  of  the  cerebrospinal  fluid  showed 
no  deviation  from  the  normal  control.  In  all,  14  fluids  from 
such  cases  were  analyzed  by  me.  Average  formula:  S.: 
W.  R.  - ;  C.  S.  R:  W.  R.  - ;  Gl.  -  ;  PL  -  ;  Feh.  +. 

Paramyoclonus  Multiplex. — In  one  instance  of  this  very 
interesting  disease  analyzed  at  the  Neurological  Institute 
the  findings  were  in  every  way  negative.  It  is  not  amiss  here 
to  mention  a  case  observed  in  the  Montefiore  Home,  that 
developed  after  surgical  interference  with  the  thyroid  gland. 


MISCELLANEOUS   AFFECTIONS  115 

It  is  probable  that  in  this  case  the  parathyroids  were  affected 
by  the  procedure.  Feeding  with  raw  thyroid  gave  no  relief. 
So  far  as  I  know  no  serologic  work  has  been  done  on  the 
disease. 

Vasotrophic  Disorders 

Symmetric  Gangrene  (Raynaud's  Disease). — In  2  out  of 
6  cases  a  positive  Wassermann  was  repeatedly  obtained  on 
the  serum.  Although  both  patients  denied  having  knowl- 
edge of  the  infection,  both  promptly  improved  after  mercu- 
rial treatment.  These  patients  showed  an  absolutely  normal 
cerebrospinal  fluid.  The  other  patients  were  likewise  in  every- 
way normal  serologically.  Of  the  latter  group,  two  received 
very  small  doses  of  thyroid  extract,  with  markedly  bene- 
ficial results.  Although  this  work  is  not  a  treatise  on  thera- 
peutics, I  would,  nevertheless,  in  view  of  the  gratifying 
results  obtained,  mention  this  fact  here,  with  the  hope  that 
other  suitable  cases  of  this  disease  will  be  studied  and  treated 
in  a  similar  manner.  In  one  patient  especially  the  results 
were  particularly  interesting;  this  patient  was  about  to  have 
his  leg  amputated  (the  other  having  been  amputated  before), 
but  at  the  last  moment  he  refused  surgical  interference. 
This  patient  was  one  of  the  two  mentioned  above  as  hav- 
ing improved  so  much  that  he  walked  out  of  the  hospital, 
using  the  leg  that  was  to  have  been  removed  with  great  ease. 
Average  formula:  S.:  W.  R.  +  or-;  C.  S.  F.:  W.  R.  -  ; 
Gl.-;  PI.-;  Feh.  +. 

Scleroderma. — I  had  the  opportunity  to  analyze  7  cases  of 
this  clinical  condition.  Four  were  being  treated  by  the  late 
Dr.  Sigmund  Lustgarten.  It  is  a  very  interesting  fact  that 
every  serum  analyzed  gave  a  positive  Wassermann  reaction. 
Three  patients  had  their  serum  analzyed  more  than  once, 
with  the  same  result.  In  every  instance  the  patient  denied 
knowledge  of  the  infection,  nor  could  other  luetic  manifes- 
tations be  detected  in  any  of  them.  Although  antiluetic 
remedies  were  tried  in  4  cases,  not  the  least  change  for  the 
better  followed.  The  Wassermann  reaction  was  also  studied 
after  the  mercurialization,  without  any  abatement  of  the 
former  intensity.  The  cerebrospinal  fluid  studied  in  two 
cases  gave  no  deviation  from  the  normal.     I  believe,  from 


116      SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

the  foregoing  studies,  that  we  are  dealing  with  a  clinical 
condition  that  is  capable  of  giving  a  positive  Wassermann 
reaction  without  being  in  any  way  related  to  syphilis.  In 
one  patient  in  whom  a  tentative  diagnosis  of  scleroderma  was 
made  and  was  later  changed  to  one  of  arteriosclerosis,  the 
Wassermann  reaction  was  negative.  Average  formula: 
S.:  W.R.  +;  C.  S.  F.:  W.R.-;  GL-;  PL-;  Feh.  +. 

Erythromelalgia. — In  two  instances  the  serology  showed 
no  deviation  from  the  normal.  In  a  third  the  condition  was 
an  accompaniment  of  tabes;  this  will  be  discussed  further  on 
under  the  consideration  of  Luetic  Diseases.  Average  formula : 
S.:  W.R.-;  C.S.F.:  W.R.-;  GL-;  PI.-;  Feh.  +. 

Acroparesthesia. — This,  as  well  as  the  condition  just  con- 
sidered (erythromelalgia),  cannot,  properly  speaking,  be 
regarded  as  a  particular  disease  having  a  definite  pathologic 
basis.  The  serology  in  two  instances  analyzed  by  me  was 
normal. 

Disorders  of  Internal  Secretion 

Myxedema. — In  two  cases  the  serum  was  negative  to  the 
Wassermann  test.  The  spinal  fluid  was  not  analyzed.  Halli- 
burton had  the  opportunity  of  studying  a  fluid  from  a  case 
of  myxedema,  and  states  that  he  could  not  find  mucin. 
Whether  the  substance  present  in  the  subcutaneous  tissues 
of  the  myxedemic  is  true  mucin  is  a  point  that  has  not  been 
settled. 

Exophthalmic  Goiter. — In  one  instance  giving  a  history  of 
lues  a  positive  Wassermann  was  obtained  in  the  serum.  In 
5  others  without  any  luetic  manifestations  and  a  negative 
history  the  Wassermann  in  the  serum  was  also  negative.  The 
spinal  fluid  was  not  studied,  as  it  was  considered  unsafe  to 
perform  a  lumbar  puncture  in  these  patients. 

Acromegaly. — In  acromegaly,  as  well  as  in  gigantism,  the 
serology  as  obtained  by  me  was  normal.  In  one  instance  of 
dystrophia  adiposo-genitalis  (Frohlich)  with  syphilitic  in- 
volvement of  the  pituitary  gland  I  had  the  opportunity  to 
study  the  serology  before  and  after  treatment.  The  positive 
Wassermann  gradually  disappeared  in  the  serum,  and  the 
spinal  fluid  remained  the  same  as  before  treatment,  i.  e., 


THE    PSYCHOSES  117 

normal.  The  hemianopsia,  as  well  as  the  adiposity  and 
the  third  nerve  involvement,  improved  markedly. 

According  to  Cushing,  the  hypopituitary  individual 
shows  an  increased  tolerance  for  levulose.  In  the  Neuro- 
logical Institute  it  is  customary  to  administer  to  patients 
suspected  of  having  this  condition  1.3  gm.  of  levulose  for 
every  pound  of  weight  of  the  individual.  The  urine  is  col- 
lected in  separate  marked  containers,  and  the  time  of  the 
appearance  of  the  carbohydrate  is  observed.  In  a  patient 
with  a  normal  tolerance  a  distinct  reduction  of  Fehling's 
solution  should  be  obtained  after  the  ingestion  of  this  quan- 
tity of  levulose.  When  the  posterior  lobe  of  the  pituitary  is 
involved  in  a  pathologic  process  (posterior  pituitary  insuffi- 
ciency), much  larger  quantities  can  be  metabolized  than  those 
mentioned — 1.3  gm.  for  every  pound  body- weight  of  the 
patient. 

Mestrezat  observed  a  case  that  showed  the  clinical  picture 
of  acromegaly  in  a  patient  with  an  ovarian  cyst.  The  fluid 
gave  a  strong  reaction  with  Fehling's  solution  and  the  pres- 
sure was  increased.  Average  formula:  S.:  W.  R.  — ; 
C.  S.  F.:  W.R.-;  GL-;  PL-;  Feh.  +. 

Addison's  Disease. — The  cerebrospinal  fluid  and  the 
serum  are  normal.  Bousquet  and  Derrien  found  acetone  in 
the  cerebrospinal  fluid  of  a  patient  with  this  disease.  The 
urine  also  showed  a  marked  excess  of  acetone.  The  condi- 
tion was  fatal. 

Myasthenia  Gravis. — As  some  observers  believe  that  the 
malady  is  the  result  of  impaired  thymic  function,  it  may  prop- 
erly be  considered  here.  In  two  patients  the  serology  was 
entirely  normal.  In  one  of  these  metabolic  studies  revealed 
nothing  unusual.  Average  formula :  S.:  W.  R.—  ;  C.  S.  F.: 
W.R.-;  Gl.-;  PL-;  Feh.  +. 

THE  PSYCHOSES 

Constitutional  Inferiority. — Since  the  perfectly  normal 
man  is  very  rare  indeed,  and  as  a  standard  of  perfection 
has  not  as  yet  been  established,  a  large  number  of  human 
beings  might  be  included  in  the  class  of  inferiors.  Kraepelin 
makes  a  distinct  division  between  the  insanities  proper  and 


118      SEROLOGY   OF   NERVOUS    AND   MENTAL   DISEASES 

the  types  of  disorder  classified  under  the  head  of  constitu- 
tionally inferiors. 

In  a  paper  entitled  "A  Consideration  of  Constitutional 
Inferiority"  by  H.  W.  Wright  the  subject  is  presented  in  a 
concise  and  comprehensive  manner.  The  classification  as 
offered  by  him,  and  quoted  here  with  the  author's  permission, 
is  as  follows : 

1.  The  Psychogenic  Neuroses — (a)  Hysteric  psycho- 

ses; (6)  apprehensive  neuroses;  (c)  expectation 
neuroses. 

2.  Original  Traits — (a)   Neurasthenia;    (b)   constitu- 

tional pessimism;  (c)  constitutional  irritability; 
(d)  compulsive  insanity;  (e)  erythromania;  (/) 
impulsh'eness ;  (g)  sexual  anomalies. 

3.  Psychogenic  Personality — (a)  Congenital  criminal- 

ity or  moral  insanity;  (b)  insanity  of  the  emotions; 
(c)  dipsomania;  (d)  habitual  criminality;  (e) 
morbid  lying,  morbid  faking;  (/)  querulousness, 
habitual  doubting. 

4.  Arrested   Mental   Development — (a)    Idiocy;    (b) 

imbecility. 

In  this  broad  grouping  may  be  placed  the  backward  school- 
child,  whose  condition  has  attracted  a  great  deal  of  atten- 
tion, particularly  from  the  standpoint  of  therapy.  Among 
specimens  of  inferiority  may  be  included  the  habitual  truant, 
the  vagrant,  the  hobo,  the  tramp,  the  "Jack-of-all-trades," 
as  well  as  the  street  tough  and  his  gang. 

The  importance  of  the  foregoing  resume  of  the  classifica- 
tion of  constitutionally  inferior  individuals  becomes  appar- 
ent when  one  takes,  into  consideration  the  possibility  of  the 
development  of  a  true  deteriorating  psychosis  on  the  basis 
of  the  psychopathic  constitution.  This  subject  was  covered 
in  a  masterful  way  by  Dr.  S.  E.  Jelliffe  in  his  consideration  of 
"Predementia  Preecox"  states. 

The  manifestation  of  these  abnormalities  depends  upon 
two  factors:  first,  defects  of  heredity;  second,  environ- 
ment. In  this  exposition  of  the  subject  the  hereditary 
factor  will  receive  closer  attention,  as  the  serology  of  these 
defectives  is  frequently  altered  by  hereditary  antecedents. 


THE    PSYCHOSES  119 

The  entire  question  resolves  itself  into  the  possible  syphilitic 
factor  which  may  have  been  responsible  for  the  inferiority, 
and  recently,  also,  attention  has  been  directed  to  the  in- 
fluence internal  secretory  abnormalities  may  exert  on  certain 
predisposed  individuals.  The  significant  observation  of 
Alzheimer,  that  juvenile  paresis  not  infrequently  develops  in 
the  course  of  inferiority  on  a  constitutional  basis,  shows  that 
syphilis  in  these  cases  must  be  the  causative  factor  not  only 
of  the  paresis,  but  perhaps  also  of  the  preceding  psychosis. 
At  least  serologic  investigations  point  very  significantly 
in  that  direction.  In  12  per  cent,  of  my  cases  a  positive  serum 
Wassermann  was  obtained.  The  cerebrospinal  fluid  was 
analyzed  in  8  instances,  and,  with  the  exception  of  one  case, 
were  all  negative.  The  single  exception  gave  21  cells  per 
cubic  millimeter,  a  normal  globulin  content,  and  a  negative 
Wassermann  reaction.  The  value  of  the  negative  serum 
Wassermann  in  this  instance  is  only  of  secondary  importance. 
The  history  of  the  parents  is  much  more  significant,  regard- 
less of  the  negative  result.  Fournier  speaks  of  another  class 
that  may  properly  be  included  in  this  consideration;  these 
children  he  terms  as  "les  enfants  arrieres";  in  them  slowly 
developing  mental  and  physical  defects  manifest  themselves 
in  the  developmental  period.  In  these  children  dentition 
is  delayed,  they  begin  to  talk  late,  are  poor  scholars,  have  a 
small  vocabulary,  and  possess  a  poor  memory.  As  they  grow 
up  they  are  far  behind  their  companions,  "toujours  en 
retard,"  and  although  displaying  here  and  there  useful 
capabilities,  they  are  lacking  in  originality,  progressiveness, 
and  brilliancy.  They  are  not  necessarily  idiots  or  imbe- 
ciles— their  somatic  and  psychic  make-up  does  not  permit 
of  such  a  designation.  Syphilis  cannot  infrequently  be  held 
responsible  for  the  defect,  and  at  times  can  be  demonstrated 
physically  (teeth,  nose,  glands). 

That  internal  secretory  disturbances  produce  psychic 
manifestations  which  most  likely  belong  to  the  same  group 
of  cases  as  those  classified  under  the  head  of  Constitutional 
Inferiorities  is  becoming  more  evident,  since  completer 
studies  of  these  secretory  disturbances  can  be  found  in  the 
literature.     In  Cushing's  book  on  the  pituitary  gland  one 


120      SEROLOGY  OF    NERVOUS   AND    MENTAL   DISEASES 

meets  with  distinct  types  of  mental  inferiority  where  this 
gland  is  affected.  I  saw  two  cases  of  such  deterioration  in 
juvenile  acromegalics.  I  also  noted  a  hypothyroid  complex 
in  two  brothers,  aged  eight  and  ten  years  respectively,  who 
were  backward  in  school  and  showed  a  spastic  gait  and  a 
low  blood-pressure.  Thyroid  medication  removed  these 
stigmata  of  inferiority  in  a  very  short  time. 

The  serology  of  this  entire  group  can  be  summed  up"  under 
two  headings :  First,  those  who  give  a  positive  serum  Wasser- 
mann,  whose  parents  deny  an  infection,  and  who  give  a 
negative  Wassermann  in  their  serum.  Second,  those  whose 
parents  admit  an  infection  and  whose  serum  is  negative. 
The  spinal  fluid  is  but  rarely  involved,  but  an  analysis  of 
this  fluid  should  never  be  omitted  when  practicable. 

As  regards  the  treatment,  one  should  take  into  considera- 
tion the  fact  that  it  is  possible  for  paresis  to  develop  in  those 
cases  in  which  syphilis  can  be  held  responsible  for  the  occur- 
rence of  the  disease.  Where  the  Wassermann  proves  posi- 
tive, treatment  should  be  instituted  to  remove  the  cause  as 
soon  as  possible,  and  repeated  analyses  be  made  to  detect 
any  symptoms  of  a  recurrence. 

Idiocy  and  Imbecility. — That  some  cases  of  feebleminded- 
ness occurring  in  younger  years  depend  upon  a  hereditary 
syphilis  must  be  admitted,  although  most  children  who 
are  effected  by  an  extensive  luetic  cerebral  process  pre- 
natally,  as  a  rule,  succumb  to  the  marasmus  produced  by  the 
infection.  Only  where  the  luetic  process  is  so  mild  as  to  spare 
the  life  of  the  child  do  we  in  later  years  find  the  landmarks 
of  mental  enfeeblement  known  as  idiocy  or  imbecility.  It 
is  not  essential  for  the  hereditary  signs  of  lues  to  manifest 
themselves  in  the  form  of  somatic  symptoms;  the  display 
can  be  and  often  is,  purely  psychic.  Where  one  is  able  to 
demonstrate  pupillary  abnormalities,  the  somatic  factor 
alone  is  sufficient  evidence  of  the  cause  of  the  trouble. 
Serologic  investigation,  however,  should  take  in  the  sys- 
tematic study  of  serum  and,  where  feasible,  also  of  the  spinal 
fluid  of  the  patient  and  parents.  Plaut  went  even  so  far  as 
to  examine  the  brothers  and  sisters  of  the  patient,  and  re- 
ported very  important  findings. 


ORGANIC    PSYCHOSES  121 

That  such  analyses  wall  in  the  future  give  the  therapeutist 
much  concern  is  not  to  be  denied,  for  the  problem  in  a  child 
with  an  idiotic  mentality  with  a  history  of  lues  in  the  parents 
and  a  positive  Wassermann  in  the  serum  of  the  patient  will 
possibly  require  the  treatment  of  the  entire  family,  including 
the  patient.  Only  in  such  a  manner  can  prophylaxis  be 
established,  and  the  further  mental  deterioration  of  the  im- 
becile child  checked.  A  few  very  interesting  case  reports 
are  to  be  found  in  the  above-mentioned  book  of  Plaut  (see 
Literature).  The  material  analyzed  at  the  Neurological 
Institute  disclosed  the  relationship  of  the  syphilitic  factor 
in  the  parents  and  child  in  very  few  instances.  Very  pro- 
nounced defectives  were  studied,  as  well  as  those  who  gave 
only  slight  symptoms.  In  the  former  a  positive  Wassermann 
could  be  obtained  in  the  serum,  but  not  in  the  cerebrospinal 
fluid.  Where  the  fluid  was  also  positive  to  the  Wassermann 
test  and  showed  a  mild  pleocytosis,  the  disease  was  considered 
as  juvenile  paresis  and  will  be  given  in  a  separate  paragraph. 

There  is  no  denying  the  fact  that  in  the  future  serologic 
methods  will  shed  a  light  not  only  on  the  etiology,  but  also 
serve  as  a  guide  to  the  best  form  of  treatment.  Systematic 
serologic  analyses  on  inmates  of  institutions  for  mental  de- 
fectives will,  in  the  course  of  time,  give  sufficiently  encour- 
aging results  to  justify  not  only  the  establishment  of  sero- 
logic stations  as  a  part  of  equipment  of  such  institutions,  but 
every  child,  before  being  admitted  to  these  institutions,  will 
be  required  to  present  a  certificate  from  a  competent  serol- 
ogist  as  to  the  existence  or  non-existence  of  a  positive  Was- 
sermann reaction,  and  perhaps  a  study  of  the  cerebrospinal 

fluid. 

ORGANIC  PSYCHOSES 

Senile  and  Presenile  Dementia. — As  a  terminal  stage, 
and  as  an  accompaniment  of  a  more  or  less  generalized 
arteriosclerosis,  and  never  associated  with  syphilis,  dementia 
of  the  aged  is  a  disease  possessing  a  negative  serology. 
Although  this  condition  may  be  included  under  the  next 
subheading,  it  seems  to  me  to  deserve  a  place  for  itself.  This 
is  particularly  true  of  cases  of  presenile  dementia,  since  the 
studies  of  Alzheimer  made  it  a  clear  clinical  and  pathologic 


122      SEEOLOGY   OF   NERVOUS    AND   MENTAL   DISEASES 

entity.  Average  formula  for  both:  S.:  W.  R.  — ;  C.  S.  F.: 
W.  R.  — ;  Gl.  -  ;  Feh.  normal. 

Psychoses  Accompanying  Organic  Brain  Diseases  (Non- 
luetic). — This  varied  group  of  psychoses,  so  far  as  the 
serology  is  concerned,  depends  upon  the  factor  producing  the 
mental  abnormality.  We  are,  therefore,  confronted  with  the 
findings  that  are  obtainable  in  brain  tumors,  in  brain  ab- 
scesses, in  cerebral  hemorrhages,  and  in  extensive  cerebral 
arteriosclerosis.  Besides  these  pathologic  factors  we  must 
also  consider  the  psychosis  that  is  at  times  observed  in 
multiple  sclerosis.  In  the  order  mentioned,  we  occasionally 
find,  in  the  serology  of  brain  tumors,  a  pleocytosis;  this,  of 
course,  depends  upon  the  location  of  the  tumor,  which,  in 
order  to  furnish  a  pleocytosis,  must  be  close  enough  to  the 
meninges  in  order  to  produce  the  necessary  irritation.  Next 
to  be  considered  are  the  various  abscesses,  which  may  or  may 
not  give  a  pleocytosis,  all  depending  upon  location,  extent, 
and  integrity  of  the  abscess-wall. 

The  simple  arteriosclerotic  forms  give  an  absolutely 
negative  serology.  The  psychosis  that  is  at  times  an  ac- 
companiment of  multiple  sclerosis  gives  a  negative  serology. 
The  globulin  is,  as  a  rule,  within  the  normal,  and  Fehling's 
reduction  is  always  prompt.  In  hemorrhage  of  the  brain  one 
is  occasionally  able  to  demonstrate  altered  blood  constitu- 
ents, and  sometimes  even  the  unaltered  cells  themselves. 

The  Wassermann  reaction,  where  a  visceral  syphilis  is 
present,  will  sometimes  be  found  to  be  positive  in  the 
serum.  In  the  cerebrospinal  fluid  the  Wassermann  is 
always  negative,  except  for  those  peculiar  findings  in  which 
large  quantities  of  fluid  were  used  and  resulted  in  positive 
Wassermann  reactions  in  some  cases  of  undoubted  multiple 
sclerosis.  This  could  never  occur  where  proper  technic  and 
the  standard  Wassermann  were  employed. 

FUNCTIONAL  PSYCHOSES 

Manic  Depressive  Insanity. — Whether  during  the  manic 
stage  or  during  the  depressed  period,  one  rarely  finds  ab- 
normalities in  the  cerebrospinal  fluid.  Syphilis  of  the  other 
organs  may  be  an  accompanying  feature  and  give  a  positive 


TOXIC    PSYCHOSES  123 

Wassermann  in  the  serum;  the  fluid,  however,  is  always 
normal.  If  obtained  after  an  acute  maniacal  attack,  the  pres- 
sure may  be  increased;  the  chemical  and  biologic  findings, 
will,  however,  be  normal.  Certain  mental  phases  of  this 
disease  may  resemble  certain  psychic  disturbances  obtained 
at  times  in  general  paresis;  this  coincidence  is  discussed  in 
the  section  on  General  Paresis,  where  the  required  informa- 
tion as  to  the  serologic  differentiation  can  be  found. 

Dementia  Praecox. — The  various  forms  of  this  disease 
(hebephrenic,  catatonic,  paranoiac)  present,  as  a  rule,  a 
negative  serology.  Syphilis  may  enter  as  a  complicating 
factor  in  some  instances,  and  give  a  positive  Wassermann 
reaction  in  the  serum.  This  disease-  may  also,  in  one  of 
its  manifestations,  give  rise  to  an  uncertainty  in  the  final 
differentiation  between  it  and  general  paresis;  a  discussion 
of  this  will  be  found  under  the  head  of  the  latter  disease. 

I  have  collected  the  records  of  a  number  of  cases  of  de- 
mentia praecox  who  were  infected  with  syphilis,  and  hence 
gave  a  positive  Wassermann  reaction  in  the  serum.  The 
question  of  general  paresis  did  not  enter  into  the  considera- 
tion of  the  diagnosis,  as  the  clinical  picture  in  these  instances 
did  not  present  diagnostic  difficulties.  Average  formula: 
S. :  W.  R.  -  ;  C.  S.  F. :  W.  R.  -  ;  Gl.  -  ;  PI.  -  ;  Feh.  normal. 

Anxiety  Depression. — Here  the  serology  is  usually  nega- 
tive, except  in  the  presence  of  lues  of  the  viscera. 

Paranoid  States. — Very  little  is  known  of  the  serologic 

status  of  this  disease.    A  few  cases  of  this  condition  were 

analyzed  and  showed  a  negative  serology  in  the  serum  and 

fluid. 

TOXIC  PSYCHOSES 

Acute  Alcoholism. — This  mental  derangement  occurs  as 
the  result  of  an  acute  exacerbation  of  a  more  or  less  chronic 
condition.  Besides  this,  it  is  possible  for  an  acute  alcoholic 
hallucinosis  to  develop  in  cases  without  a  background  of 
chronic  alcoholism,  occurring  in  an  individual  whose  toler- 
ance for  alcohol  is  below  the  average,  and  one  who  has  not 
been  addicted  to  the  prolonged  use  of  alcoholic  beverages. 
Occurring  as  a  pure,  uncomplicated  toxic  psychosis,  the 
serology  is  correspondingly  negative.    With  the  aid  of  the 


124      SEROLOGY   OF   NERVOUS    AND    MENTAL   DISEASES 

iodoform  test  Schottmiiller  and  Schumm  demonstrated,  in 
acute  alcoholism,  appreciable  quantities  of  aldehyd.  This 
fact  reflects  greatly  the  degree  of  injury  to  the  meninges 
caused  by  the  overuse  of  alcohol. 

Chronic  Alcoholism. — The  serology  of  this  condition  is 
negative. 

The  Korsakoff  Syndrome. — This  mental  derangement  is 
not  necessarily  due  to  alcoholic  abuse  alone;  it  may  develop 
as  the  result  of  any  intoxication,  and  may  or  may  not  be  ac- 
companied by  polyneuritic  manifestations.  The  term  is  not 
to  be  applied  exclusively  to  those  forms  of  toxic  psychoses 
that  are  associated  with  nerve  involvement,  but  is  also  ap- 
plicable to  a  pure  psychosis  without  such  accompaniment. 
As  it  is  at  times  difficult,  in  certain  cases  of  this  psychosis,  to 
differentiate  between  this  and  general  paresis,  the  im- 
portance of  serologic  aid  will  become  apparent,  as  this  alone 
can  definitely  decide  the  question.  The  differentiation  will 
be  described  in  the  section  on  General  Paresis.  The  real 
difficulty  arises  when  a  coincident  visceral  syphilis  com- 
plicates the  toxic  psychosis.  Here  very  careful  weighing 
of  the  individual  clinical  and  laboratory  data  are  necessary 
in  order  to  avoid  error  in  the  diagnostic  interpretation  of  the 
complex.  In  such  cases  the  serum,  if  positive,  will  have  to 
be  judged  not  only  by  the  fact  that  it  is  positive,  but  the 
degree  of  inhibition  and  other  characteristics  of  a  positive 
serum  reaction  will  have  to  be  considered  before  the  possi- 
bility of  general  pareis  is  excluded.  This  difficulty  is  only 
partially  removed  by  a  contemporaneous  study  of  the  cerebro- 
spinal fluid.  The  finding  of  negative  fluids  in  general  paresis 
is  by  no  means  an  impossibility,  although  their  occurrence 
is  rare.  Average  formula:  S.:  W.  R.—  ;  C.  S.  F.:  W.  R.  —  ; 
Gl.  -  ;  PL  -  ;  Feh.  normal. 

Lead  Psychosis. — This  psychosis  may  present  acute  and 
chronic  manifestations.  The  diagnosis  is  not  furthered  by  a 
serologic  investigation,  as  the  cerebrospinal  fluid  in  2  cases 
of  the  chronic  form  showed  no  deviation  from  the  normal 
findings.  The  presence  of  lead  could  not  be  demonstrated 
by  Bernard  and  Troisier  in  a  case  of  chronic  plumbism. 
The  diagnosis  can  be  facilitated  considerably  by  a  mor- 


TOXIC   PSYCHOSES  125 

phologic  study  of  the  red  blood-corpuscles,  which  in  such 
cases  will  frequently  show  the  characteristic  basophilic 
granulations. 

Coal-tar  Psychosis  (After  Prolonged  Use). — After  the 
use  of  large  doses  of  antipyrin  and  acetanilid  a  patient 
developed  an  acute  mania  which  gave  place  to  a  coma  that 
lasted  for  ten  days.  After  eliminative  treatment  the  condi- 
tion disappeared  completely.  The  serology  of  the  serum 
and  fluid  was  entirely  negative. 

Morphin  Psychosis  (After  Prolonged  Use). — The  serology 
is  entirely  negative. 

Infective  exhaustive  psychoses  occurring  in  the  course  of — 

Tuberculosis. — For  the  occurrence  of  a  psychic  derange- 
ment in  the  course  of  tuberculosis  (pulmonary,  miliary,  etc.), 
it  is  not  absolutely  essential  for  the  tubercle  bacillus  to 
involve  the  meninges.  Hence  the  finding  of  the  bacillus  in 
the  cerebrospinal  fluid  is  to  be  included  among  the  excep- 
tions, rather  than  among  the  expected  findings.  When 
these  bacilli  are  demonstrated  in  the  fluid  during  the  course 
of  a  pulmonary  tuberculosis,  the  aspect  of  the  clinical  condi- 
tion becomes  altered  at  once,  and  the  gravity  of  the  situation 
is  correspondingly  increased.  Such  a  psychic  derangement 
requires  considerable  diagnostic  acumen  in  order  to  be  able 
to  differentiate  between  that  which  is  exhaustive  and  that 
which  is  caused  by  the  meningeal  involvement  by  the 
tubercle  bacillus.  It  is,  perhaps,  better  judgment  to  con- 
sider the  psychic  disturbance  in  such  a  coincidence  as  a 
product  of  the  activities  of  both  factors — infective  and 
exhaustive.  With  the  exception  of  cases  with  meningeal 
involvement,  the  serology  is  negative. 

Typhoid. — On  several  occasions  the  bacillus  of  Eberth 
was  demonstrated  in  the  fluid  from  patients  with  this  affec- 
tion. The  psychosis  that  at  times  accompanies  this  disease 
may  make  manifest  the  presence  of  the  bacterium  in  the 
fluid  without  increasing  the  dangers.  Patients  who  gave 
positive  morphologic  and  cultural  evidence  as  to  the  pres- 
ence of  this  bacillus  in  the  cerebrospinal  fluid  showed  in 
most  instances  no  appreciable  pleocytosis,  nor  were  other 
cardinal  signs  of  a  meningitis  found.    It  is  more  likely  that 


126      SEROLOGY   OP   NERVOUS    AND    MENTAL   DISEASES 

the  phenomena  responsible  for  the  psychosis,  when  present, 
are  purely  chemical;  in  other  words,  the  absorption  of  tox- 
ins is  responsible  for  the  patient's  deranged  mentality. 
These  toxic  substances,  again,  are  not  necessarily  entirely 
the  by-product  of  the  life  of  the  bacillus;  it  is  highly  prob- 
able that  the  increased  metabolism  of  the  febrile  state  is  in 
itself  capable  of  giving  rise  to  a  deranged  mental  activity 
as  a  result  of  the  absorption  of  body  toxins. 

Postpartum  Infections. — These  infections  are  very  prone 
to  give  rise  to  meningeal  irritations,  and,  when  present, 
will  give  the  serology  of  a  meningitis.  On  the  other  hand, 
chronic  postpartum  infections,  those  that,  as  a  rule,  do  not 
prove  fatal  in  a  week  or  two,  may  give  rise  to  a  psychosis 
that,  from  an  etiologic  point  of  view,  is  purely  exhaustive, 
and  directly  dependent  upon  the  original  infection  of  the 
birth-canal.  So  far  as  I  was  able  to  ascertain  the  serology  of 
these  latter  cases  is  entirely  negative. 

Traumatic  Psychosis. — The  proper  interpretation  of 
this  clinical  condition  gives  rise  at  times  to  considerable 
trouble.  The  correct  diagnosis  can  still  further  be  deferred 
by  the  coexistence  of  syphilis  with  a  psychosis  caused  by 
physical  trauma.  In  such  a  case  the  positive  serum  Was- 
sermann  with  a  few  cells  in  the  cerebrospinal  fluid  (border- 
line count)  is  frequently  sufficient  to  mislead  the  most 
skilled  observer. 

I  had  the  opportunity  to  analyze  such  patients  serologically, 
some  presenting  diagnostic  difficulties  that  could  not  be 
overcome  until  a  prolonged  observation  cleared  up  the  doubt. 
Three  patients  presented  the  following  findings: 

A  commercial  man  of  forty-two,  married;  wife  had  two  mis- 
carriages; no  living  children.  Patient  sustained  an  injury  to 
the  head  as  the  result  of  a  fall.  Upon  examination  pre- 
sented lively  knee  reflexes;  left  pupil  irregular;  reactions 
normal;  slight  speech  disturbance;  poor  memory  as  to  the 
circumstances  attending  his  accident,  and  general  restless- 
ness. Admitted  lues.  The  Wassermann  in  the  serum  was 
positive;  the  cerebrospinal  fluid  showed  a  border-line  count 
(12  lymphocytes  per  c.mm.)  and  a  few  degenerated  red 
blood-corpuscles.     Globulin,  Fehling,  and  Wassermann  nor- 


TOXIC    PSYCHOSES  127 

mal.  For  the  Wassermann  in  the  cerebrospinal  fluid  1  c.c. 
was  used  in  order  to  exclude  the  chances  of  a  faulty  negative 
Wassermann;  in  other  words,  opportunity  was  offered  for 
the  fluid  to  react  positively.  The  fact  that  the  result  was 
negative  with  1  c.c.  of  fluid  put  the  clinicians  on  their  guard, 
and  the  final  conclusion  arrived  at  later  was  a  diagnosis  of 
traumatic  psychosis  and  not  of  general  paresis. 

In  another  patient  who  was  thrown  from  a  carriage  the 
following  history  was  obtained:  Patient,  thirty-six  years 
old,  a  coal-broker;  married;  no  children;  wife  had  no  mis- 
carriages. At  nineteen  the  patient  had  been  treated  for 
some  genito-urinary  trouble  for  two  years;  was  given  drops 
and  inunctions.  Never  had  an  ulcer  on  the  glans.  Remem- 
bers having  a  urethral  discharge.  After  the  injury  patient 
was  comatose  for  four  days.  Had  bleeding  under  the  con- 
junctivae and  from  the  ears  and  nose.  A  few  months  after  a 
more  or  less  complete  recovery  the  patient  became  absent 
minded,  his  attitude  toward  his  family  changed,  and  he  be- 
came neglectful  of  his  business  duties  and  showed  a  slight 
amnesia.    The  serology  in  his  case  was  as  follows: 

Serum  Wassermann  negative;  cerebrospinal  fluid  Was- 
sermann negative;  globulin  normal;  cells,  a  few  lympho- 
cytes and  a  moderate  number  of  red  blood-corpuscles. 
It  was  believed  for  a  time  that,  in  view  of  the  history  of  two 
years'  treatment  and  the  peculiar  change  in  the  entire  atti- 
tude of  the  patient,  the  diagnosis  of  general  paresis  would 
be  a  plausible  one.  The  negative  serology  and  the  subse- 
quent course  of  the  disease  showed  the  true  nature  of  the 
malady. 

In  a  third  patient  the  following  history  was  obtained: 
A  broker,  aged  thirty-two,  separated  from  his  wife.  Patient 
was  perfectly  well  until  October,  1910.  Following  an  ac- 
cident he  became  dizzy,  had  a  convulsion,  and  soon  passed 
into  a  delirious  state,  for  which  he  showed  an  isolated  am- 
nesia. When  admitted  to  the  hospital  (Ward's  Island)  he 
was  quite  elated,  had  no  delusions  and  hallucinations,  was 
inclined  to  be  talkative,  but  coherent,  and  his  answers  were 
always  to  the  point.  His  orientation  was  good  and  he 
showed  no  defect  of  memory.     He  was  somewhat  expansive, 


128      SEROLOGY    OF   NERVOUS   AND   MENTAL   DISEASES 

but  there  was  considerable  basis  for  his  ideas,  and  it  was 
difficult  to  demonstrate  absurdity  or  fiction. 

During  his  stay  in  the  hospital  the  patient  was  quiet  and 
well  behaved,  but  still  maintained  his  former  expansive 
ideas,  which  were  probably  exaggerated,  but  not  entirely 
absurd.  He  was  at  all  times  amnesic  for  the  acute  period  of 
his  illness.  At  one  time  it  was  thought  that  the  patient 
suffered  from  general  paresis  because  of  the  history  of  syph- 
ilis, coarse  tremor  of  the  tongue,  and  on  a  previous  occasion 
the  limited  range  of  his  pupillary  reaction;  before  his  dis- 
charge his  physical  status  revealed  no  neurologic  abnormali- 
ties, and,  moreover,  fluid  withdrawn  by  lumbar  puncture 
proved  negative. 

His  serology  was  as  follows:  Wassermann  reaction  in 
serum  and  cerebrospinal  fluid  negative;  globulin  normal; 
cells,  one  lymphocyte  per  c.mm.    Fehling's  reduction  prompt. 

The  serology  in  traumatic  psychosis,  as  can  be  seen  from 
the  foregoing  exposition,  is  in  itself  not  always  conclusive; 
it  is,  therefore,  necessary,  in  some  instances,  to  wait  until 
further  clinical  signs  develop  before  a  final  conclusion  is  per- 
missible. Although  the  findings  are,  as  a  rule,  negative,  it  is 
frequently  possible,  in  recent  and  in  old  traumatic  cranial 
conditions,  to  demonstrate  an  increase  in  the  cerebrospinal 
pressure,  with  an  increased  amount  of  spinal  fluid.  Although 
fairly  constantly  present,  it,  nevertheless,  cannot  be  con- 
sidered as  pathognomonic  of  the  above-described  condition. 
Average  formula :    S. :  W.  R.  -  ;  C.  S.  F. :  W.  R.  -  ;  Gl.  -  ; 

PL-;  Feh.  +. 

INTOXICATIONS 

Metabolic. — As  a  result  of  changes  in  the  metabolic 
processes  in  the  body,  certain  organic  substances  may  ap- 
pear in  the  cerebrospinal  fluid  due  to  faulty  metabolization. 
We  have,  therefore,  an  accumulation  of  carbamid  in  uremia; 
of  glucose,  acetone,  and  diacetic  acid  in  diabetic  intoxica- 
tion ;  of  lactic  acid  in  eclamptic  seizures,  and  of  bile-products 
in  icteric  states. 

Uremic. — According  to  Mestrezat  (see  Literature),  there 
are  two  different  responses  to  be  observed  in  the  cerebro- 
spinal fluid,  which  depend  upon  the  renal  involvement  in 


INTOXICATIONS  129 

question.  In  case  of  mineral  impermeability  (to  chlorids), 
an  accumulation  of  chlorids  in  the  body  causes,  besides  the 
classic  anasarcas,  an  appreciable  increase  in  the  chlorid 
content  in  the  cerebrospinal  fluid,  without  a  corresponding 
increase  in  the  urea  content.  The  cases  that  present  a  renal 
impermeability  to  nitrogen,  with  an  accumulation  of  nitrogen 
products  of  an  excretory  nature  in  the  body,  are  the  forms 
of  renal  insufficiency  that  give  rise  to  uremic  states.  The 
physiologic  limit  of  the  urea  content  in  the  cerebrospinal 
fluid  is  1  gm.  or  less  per  100  c.c,  hence  the  urea  content  of 
patients  who  are  on  the  verge  of  or  are  undergoing  a  uremic 
attack  may  show  2  or  more  grams.  The  cases  cited  by  this 
author  are  as  follows: 

Delirium  in  an  arteriosclerotic  patient,  urea  in 

cerebrospinal  fluid 1.22  per  cent. 

Coma,  alcoholic  Bright's 1.50       " 

Delirium,  epileptic  seizures  in  old  hemiplegic.  .   2.31        " 
Coma  in  an  arteriosclerotic 2.57       " 

In  25  autopsies  without  involvement  of  the  sensorium, 
with  and  without  renal  symptoms,  the  highest  amount 
found  was  0.95  gm.  of  urea  per  100  c.c.  of  fluid.  Widal 
and  Froin  were  able  to  demonstrate  as  much  as  4.5  per  cent, 
of  urea  in  the  fluid  of  a  patient  with  nephritis  and  in  a  uremic 
attack.  Mestrezat  is  of  the  opinion  that  a  cerebrospinal 
fluid  with  a  urea  content  of  3  per  cent,  or  more,  associated 
with  a  uremic  state,  is  of  the  gravest  prognosis,  ending,  as  a 
rule,  in  death.  The  remaining  serology  is  generally  negative, 
with  the  exception  of  those  cases  complicated  by  syphilis. 

Diabetic. — In  two  cases  of  diabetic  coma  I  was  able  to 
demonstrate  acetone  in  sufficient  quantity  to  give  the  iodo- 
form reaction.  After  rallying  slightly  both  patients  died. 
The  quantity  of  glucose  in  the  spinal  fluid  is  correspond- 
ingly increased,  and  may  show  as  much  as  18  gm.  of  this 
substance  per  liter  of  spinal  fluid.  The  increase  of  this 
substance  in  the  spinal  fluid  may  be  caused  either  by  the 
hyperglycemia  and  increased  permeability  of  the  choroid 
plexus,  or  by  a  disturbance  of  the  glycoregulatory  apparatus. 
Diacetic  acid  is  obtained  rarely,  and  when  found,  signifies 
a  profound  intoxication. 


130      SEROLOGY   OF   NERVOUS    AND    MENTAL    DISEASES 

Eclamptic. — In  this  condition  the  findings  in  the  cerebro- 
spinal fluid  reflect  greatly  upon  the  role  played  by  the 
renal  integrity.  The  increase  in  chlorids  found  in  the 
eclamptic  states  is  similar  to  some  forms  of  spinal  fluid  find- 
ings associated  with  anasarca.  Besides  this,  various  authors 
claim  to  have  found  appreciable  quantities  of  lactic  acid. 
For  the  detection  of  this  substance  Reichmann  suggests 
the  following  method:  10  c.c.  of  the  spinal  fluid  are  treated 
with  5  parts  of  95  per  cent,  alcohol.  This  is  permitted  to 
extract  for  twelve  hours,  and  is  then  filtered  and  the  residue 
washed  with  hot  water  repeatedly.  The  alcohol  extract 
is  collected  in  toto  with  a  little  hot  absolute  alcohol;  this  is 
filtered,  the  filtrate  is  condensed  on  a  warm  water-bath  to 
dryness,  and  the  residue  treated  with  3  drops  of  TV  normal 
H2SO4;  to  this  is  added  about  10  c.c.  of  ether  and  the  mix- 
ture vigorously  shaken.  To  a  very  dilute  solution  of  Fe2Cl6 
(one  drop  of  the  iron  chlorid  solution  to  20  c.c.  of  water) 
in  two  test-tubes  (one  as  a  control)  add  the  ether  extract  to 
one  of  them.  If  lactic  acid  is  present,  the  solution  in  the 
test  turns  a  pale  yellow,  showing  a  distinct  difference  as 
compared  with  the  control  tube. 

Icteric. — The  chief  change  in  the  spinal  fluid,  as  well  as  in 
the  serum,  is  in  the  color.  Besides  this,  with  proper  chemical 
tests,  one  may  find  one  or  the  other  constituent  of  the  bile. 
The  most  interesting,  and,  from  a  serologic  point  of  view,  the 
most  important,  occurrence  is  the  behavior  of  sera  from 
jaundiced  patients  to  the  Wassermann  reaction.  It  is  by  no 
means  rare  to  obtain  a  positive  reaction  in  patients  suffering 
from  profound  hepatic  involvement  without  giving  the 
slightest  cue  to  the  existence  of  lues.  I  had  the  opportunity 
to  follow  up  such  cases  to  the  end  without  having  been  able 
to  demonstrate  postmortem  any  of  the  changes  usually  ob- 
tained with  syphilis.  This  observation  suggested  to  me  an 
experiment  which  proved  to  me  that  the  appearance  of 
bile-products  in  the  patient's  serum  may  give  rise  to  a  non- 
specific inhibition.  To  the  serum  from  a  patient  who  on 
many  occasions  served  as  the  negative  control  I  have  added 
gradually  increasing  quantities  of  fresh  ox-gall.  At  a  certain 
concentration    the    reaction    proved  strongly  positive  for 


INTOXICATIONS  131 

twenty-four  hours  in  the  incubator.  In  previous  writings  I 
have  repeatedly  pointed  out  the  possibility  of  obtaining 
such  a  result  without  syphilis  being  present.  The  spinal 
fluid  is  less  subject  to  such  a  pseudo-result,  perhaps  because 
the  concentration  of  the  bile-products  in  the  cerebrospinal 
fluid  is  insufficient  to  produce  this  reaction.  Colleagues  have 
also  related  similar  experiences,  having  on  several  occasions 
obtained  positive  Wassermann  reactions  on  sera  from 
patients  with  carcinoma  of  the  liver.  In  one  of  my  obser- 
vations the  positive  Wassermann  reaction  appeared  after 
a  secondary  involvement  of  the  liver  by  a  carcinomatous 
process,  the  reaction  before  this  being  absolutely  negative. 

Extraneous. — Lead. — The  serology  of  this  form  of  in- 
toxication was  practically  covered  in  dealing  with  lead 
psychosis. 

Mercury. — In  acute  mercurial  intoxication  traces  of  this 
metal,  together  with  a  mild  pleocytosis,  were  found  in  the 
cerebrospinal  fluid. 

Carbon  Monoxid. — In  a  case  where  suicide  was  attempted 
with  illuminating  gas  the  serologic  analysis  showed  an 
increase  of  albumin  in  the  spinal  fluid  and  a  pleocytosis  con- 
sisting of  80  per  cent,  of  polynuclear  elements.  Thin  fila- 
ments were  seen  in  the  fluid,  suggestive  of  fibrin.  After 
twelve  days  the  pleocytosis  disappeared  entirely  (Legry  and 
Duvoir) . 

Atropin. — An  excess  of  albumin  was  obtained  in  a  case  of 
intoxication  with  this  alkaloid. 

Manganese.— A  peculiar  form  of  intoxication  was  observed 
by  Dr.  L.  Casamajor  among  men  who  work  in  zinc  mines. 
The  ore  is  combined  with  manganese,  which,  in  the  course 
of  separation,  exists  as  a  very  fine  powder.  The  patients 
showed,  among  other  symptoms,  a  gait  similar  to  that  of 
paralysis  agitans.  The  cerebrospinal  fluid  was  entirely 
negative. 


PART   III 


THE    SEROLOGY    OF    NERVOUS    AND   MENTAL 
DISEASES    OF    LUETIC    ORIGIN 

TABES  DORSALIS 

In  addition  to  the  individual  laboratory  findings,  the 
serology  of  this  disease  will  also  embrace  the  significance  and 
interpretation  of  the  different  serum  and  spinal-fluid  phe- 
nomena encountered  in  the  various  types  of  syphilitic  in- 
volvement of  the  central  nervous  system.  It  is  perhaps  bet- 
ter to  discard  the  old  terms,  "para"  and  "meta,"  as  applied 
to  syphilis,  and  to  consider  tabes,  as  well  as  other  nervous 
diseases  caused  by  the  Treponema  pallidum,  as  syphilis  pure 
and  simple.  Noguchi  demonstrated  the  presence  of  the 
Treponema  pallidum  in  the  brains  of  patients  with  general 
paresis,  as  well  as  in  the  spinal  roots  of  one  patient  suffering 
from  tabes. 

In  the  serologic  consideration  of  tabes,  particular  stress 
will  be  laid  upon  certain  phenomena  that  have  proved  of 
great  utility  from  a  diagnostic,  therapeutic,  and  prognostic 
viewpoint.  These  manifestations  will  be  referred  to  repeat- 
edly in  dealing  with  this  part  of  the  serology  of  the  luetic 
nervous  disease. 

For  the  clinical  interpretation  of  the  various  neurologic 
entities  of  which  this  section  treats  I  am  greatly  indebted 
to  the  Medical  Officers  of  the  Neurological  Institute  for  their 
hearty  cooperation.  The  routine  serologic  examinations 
performed  on  the  great  majority  of  patients  who  apply 
to  the  Institute  for  medical  advice  showed  that  syphilis  of 
the  nervous  system  may  exist  for  many  years  without  being 

132 


TABES   DORSALIS  133 

suspected  by  the  physicians  who  had  previously  treated  the 
patient.  Vague  pains  and  gastric  disturbances  are  often 
treated  for  rheumatism  and  chronic  stomach  catarrh,  and 
it  is  not  until  the  serologic  investigation  discloses  the  true 
origin  of  the  pains  and  the  real  significance  of  the  stomach 
trouble  that  the  etiology  becomes  clear.  Some  of  these  cases 
were  differentiated  from  non-luetic  diseases,  at  first  with 
difficulty,  but  when  the  serology  proved  to  be  positive,  there 
was  no  longer  room  for  doubt.  The  juvenile  form  of  tabes 
also  offered  great  opportunity  for  errors  in  diagnosis.  That 
syphilitic  parents  are  capable  of  producing  in  their  offspring 
unquestionable  locomotor  ataxia  has  been  proved  beyond 
doubt.  The  youngest  case  of  tabes  observed  in  the  Neuro- 
logical Institute  was  in  a  girl  of  six. 

In  the  form  of  tabes  which  is  monosymptomatic  the  diag- 
nosis without  serologic  investigation  would  be  made  only  with 
extreme  difficulty.  It  seems  that  spinal  fluid  changes  are 
almost  as  constant  in  tabes  as  is  the  Argyll-Robertson  pupil 
or  the  absent  knee-jerks,  and  it  is,  moreover,  a  gratifying 
coincidence  that  where  the  clinical  diagnosis  is  most  obscure 
and  difficult,  the  laboratory  is  frequently  able  to  furnish 
weighty  evidence.  It  is  needless  to  say  that,  so  far  as  the 
diagnosis  of  tabes  dorsalis  is  concerned,  the  laboratory  does 
not  play  an  active  part,  but  it  must  be  remembered  that  the 
serologic  investigation  in  tabes  is  not  always  conducted  for 
the  purpose  of  clinching  the  diagnosis,  but,  on  the  contrary, 
from  my  experience,  the  reports  are  more  often  desired  for 
the  purpose  of  gaging  the  treatment.  Occasionally  prog- 
nostic suggestions  are  looked  for  from  the  laboratory,  or 
the  fluid  is  submitted  for  analysis  in  order  to  ascertain 
the  possible  transition  of  one  luetic  nervous  disease  to 
another. 

The  task  of  establishing  types  or  laboratory  standards 
for  this  disease  required  abundant  material,  and  the  results 
obtained  had  to  be  grouped  together  with  the  clinical  diag- 
noses furnished  after  the  reports  were  submitted  to  the 
physician  in  charge.  These  standards  or  types  will  be  spoken 
of  under  the  various  headings  of  "usual  serologic  type," 
"hyperlymphocytic  type,"  "negative  type,"  etc.    In  making 


134      SEROLOGY  OF   NERVOUS    AND    MENTAL   DISEASES 

this  classification  no  hard-and-fast  rules  are  laid  down; 
the  terms  "always"  and  "never"  are  not  used,  and  it  is  taken 
for  granted  that  allowance  will  be  made  for  exceptional  oc- 
currences. It  is  needless  to  emphasize  the  fact  that  in  the 
compilation  and  classification  of  the  various  standards  the 
greatest  number  of  cases  established  the  "usual  serologic 
type";  that  the  exceptionally  high  cell  count  suggested  the 
"hyperlymphocytic  type,"  etc.  The  serology  of  the  largest 
number  of  cases  of  tabes  is  to  be  observed  in  the  "usual 
serologic  type,"  which  will  first  be  considered. 

The  "Usual  Serologic  Type"  of  Tabes 
In  by  far  the  greater  number  of  cases  of  tabes  the  cerebro- 
spinal fluid  gives  a  negative  Wassermann  reaction.  In 
speaking  of  the  greatest  number  of  cases,  I  am  considering 
the  results  obtained  from  a  study  of  425  cerebrospinal  fluids 
from  various  tabetics.  The  serum  Wassermann  is  more 
often  positive  than  negative.  The  globulin  content  of  the 
cerebrospinal  fluid  is  generally  negative,  an  excess  reaction 
in  this  type  being  seldom  encountered.  I  do  not  consider 
those  cases  that  may  give  a  trace  of  globulin.  The  cell 
count  ranges  from  25  to  95,  the  two  extremes,  25  and  95, 
being  rather  the  exception  than  the  rule.  The  majority  of 
fluids  gave  a  cell  count  that  ranged  between  37  and  73  cells 
per  cubic  millimeter.  This  observation  shows  that  the 
serology  of  the  form  of  tabes  which  I  designate  as  the  "hy- 
perlymphocytic type"  may  include  also  specimens  that 
show  no  globulin  excess,  as  well  as  a  negative  Wassermann 
reaction,  in  the  cerebrospinal  fluid,  a  fact  to  be  remembered 
when  studying  the  "hyperlymphocytic  type."  Clinically, 
there  is  nothing  to  mark  this  serologic  form  of  tabes;  in  fact, 
the  first  intimation  that  the  patient  is  suffering  from  this 
laboratory  type  of  disease  is  had  when  the  rachicentesis 
reveals  meningeal  involvement.  It  is  to  be  noted  that  these 
designations  merely  express  the  serology  of  the  malady, 
which,  as  a  laboratory  entity,  may  have  little  in  common 
with  the  evidences  observed  during  the  course  of  the  disease, 
particularly  in  this  type  of  serum  and  fluid  analysis.  The 
serologic  formula  of  the  "usual  serologic  type"  is  as  follows: 


THE   HYPERLYMPHOCYTIC  TYPE   OF  TABES 


135 


Sebum 

Wassermann 

Reaction. 

Fluid 

Wassermann 
Reaction. 

Globulin. 

Pleocytosis. 

Reduction  op 
Fehlinq's. 

Positive. 

Negative. 

Normal. 

From  25  to 
95. 

Always 
prompt. 

The  cells  number  98  per  cent,  of  lymphocytes. 


THE    "HYPERLYMPHOCYTIC   TYPE"   OF  TABES 

It  may  generally  be  accepted  as  a  fact  that  the  more 
manifest  the  active  evidences  of  the  disease,  and  the  more 
evident  the  painful  phenomena,  the  greater  is  the  cell  count 
in  the  cerebrospinal  fluid.  This  should  not,  however,  be 
accepted  as«  an  invariable  rule  in  the  "hyperlymphocytic 
type"  of  tabes,  for  exceptions  occur;  e.  g.,  very  active  signs 
of  tabes  may  occur  without  a  corresponding  cellular  in- 
crease, and  tabetics  who  are  comparatively  comfortable 
may  show  hundreds  of  cells.  As  has  previously  been  stated, 
these  designations  apply  to  the  majority  of  observations,  and 
nowhere  in  this  study  of  the  serology  of  nervous  and  mental 
diseases  are  the  terms  "always"  and  "never"  made  use  of. 
In  the  majority  of  instances,  where  the  cell  count  in  the 
cerebrospinal  fluid  is  high,  a  positive  Wassermann  reaction 
in  the  serum  will  also  be  obtained.  This  finding,  as  an  ac- 
companiment of  the  "hyperlymphocytosis,"  is  a  fairly  con- 
stant one — in  my  experience  it  occurs  in  94  per  cent. 

With  the  higher  cell  counts  one  also  encounters  an  excess 
of  globulin,  all  of  which  point  to  the  existence  of  a  more  or 
less  active  meningeal  process.  The  spinal  fluid  Wassermann 
is  positive  in  about  one-half  of  the  cases  of  this  type.  The 
pleocytosis  averages,  as  a  rule,  less  than  100  cells  per  c.mm., 
although  here  and  there  one  may  find  as  many  as  200  and 
even  300  cells  per  c.mm.  These  findings  are,  however,  the 
exceptions,  and  cannot  be  regarded  as  establishing  the  upper 
limit  of  the  pleocytosis  of  this  serologic  variety  of  tabes. 

Not  infrequently  one  encounters  what  may  be  termed 
the  intermediary  variety  of  this  form  of  tabes  and  the 
"usual  serologic  type,"  the  connecting  link  being  the  positive 
globulin  findings  in  the  fluid,  the  Wassermann  reaction  being 


136      SEROLOGY   OP   NERVOUS    AND    MENTAL   DISEASES 


negative  in  the  fluid  and  positive  in  the  serum.  Because  of 
the  usually  high  cell  count — over  60 — this  class  of  cases  may, 
for  the  sake  of  brevity,  be  included  in  the  "hyperlymphocytic 
type,"  with  a  consequent  reduction  of  the  positive  fluid 
Wassermann  to  54  per  cent,  of  the  cases. 

Very  exceptionally  the  pleocytosis  may  reach  as  high  as 
210  and  268  cells  per  c.mm.  These  figures  represent  actual 
observations  on  two  cases;  the  serum  Wassermann  and  the 
fluid  Wassermann  were  positive,  an  excess  of  globulin  being 
obtained  in  the  latter.  In  two  other  instances  the  cell  count 
was  192  and  240  respectively,  but  the  fluid  Wassermann  was 
negative.  The  cells  encountered  were  lymphocytes,  with  an 
occasional  polynuclear  or  a  polymorphonuclear  cell.  The 
lower  count  fluids  presented  a  uniform  lymphocytic  picture. 

The  serologic  formula  of  the  "hyperlymphocytic  type"  is 
as  follows: 


Serum 

Wassermann 

Reaction. 

Fluid 

Wassermann 

Reaction. 

Globulin 

Pleocytosis. 

Reduction  of 
Fehling's. 

Positive,   as 
a  rule. 

Positive    in 
54  per 
cent,  of 
cases. 

Excess. 

60  to  96 
(and  more). 

Always  prompt. 

The  "Negative  Type"  of  Tabes 
The  designation  "negative  type"  is  applicable  to  a  very 
small  number  of  cases  presenting  an  absolutely  normal 
serology.  In  my  series  only  30  cases  gave  these  findings, 
which  is  equivalent  to  about  7  per  cent,  of  the  material 
analyzed.  There  are  instances,  however,  that  are  almost 
negative,  and  differ  from  the  absolutely  "negative  type" 
in  that  they  present  a  more  or  less  insignificant  pleocytosis, — 
from  12  to  even  32  cells  per  c.mm., — the  remainder  of  the 
serology  being  entirely  negative. 

It  is  well  to  note  at  this  point  that  although  the  "hyper- 
lymphocytosis"  may  be  taken  as  proof  of  the  existence  of  a 
meningeal  irritation,  the  "negative  type"  serology,  on  the 
other  hand,  is  significant  of  the  absence  of  such  irritation,  and 
indicates  the  existence  of  a  more  or  less  purely  degenerative 


THE  "  NEGATIVE  TYPE  "  OF  TABES        137 

process.  It  must  be  borne  in  mind  that  some  tabetics  with 
a  "negative  type"  serology  nevertheless  occasionally  present 
the  clinical  picture  of  an  active  process,  particularly  pain, 
and  respond  readily  to  proper  therapy.  Although  it  may  be 
difficult  to  reconcile  negative  serologic  findings  with  a  process 
that  indicates  an  active  ganglionitis,  it  is,  nevertheless, 
plausible  to  believe  that  the  active  process  may  be  confined 
to  a  locality  which  prevents  spinal  fluid  contamination.  It 
may  also  be  possible  that  the  exudative  process  affecting  the 
ganglion  in  the  intervertebral  foramen  is  prevented  from 
producing  a  pleocytosis  in  the  cerebrospinal  fluid  by  the 
formation  of  a  barrier  during  the  process  of  repair  in  the 
course  of  a  previous  inflammation.  This  latter  will  wall  off 
the  laboratory  signs  of  inflammatory  manifestations,  in- 
cluding the  pleocytosis,  from  the  subarachnoid  space.  Thus 
may  be  explained  the  presence  of  active  symptoms  in  a 
patient  whose  fluid  presents  a  moderate  cellular  increase  or 
even  no  increase  at  all.  On  the  other  hand,  the  nervous 
elements  between  the  bony  walls  of  the  foramen  and  the 
nervous  structures  contained  therein  are  so  closely  crowded 
that  but  little  exudation  or  other  inflammatory  manifesta- 
tion is  necessary  to  produce  pressure  and,  hence,  pain. 

The  pleocytosis  seen  in  herpes  zoster  rarely  gives  more 
than  40  or  50  cells  per  c.mm.,  and,  furthermore,  the  absence 
of  a  cellular  increase  in  this  malady  is  of  very  frequent 
occurrence.  Since  more  elaborate  anatomic  studies  are  lack- 
ing, one  may  select  any  of  the  contentions  just  set  down  or 
formulate  another  for  himself  as  experience  may  teach. 

The  "relatively  negative  type"  of  tabes  presents  a  border- 
line cell  count,  and  may  occasionally  show  but  25  cells  per 
c.mm.  Here  and  there  I  observed  what  may  be  considered 
the  upper  cell  limit  of  this  type,  and  counted  30  and  32  cells. 
The  remainder  of  the  serology  is  entirely  negative.  This 
"relatively  negative  type"  was  obtained  in  21  per  cent,  of  the 
cases  studied.  There  is  another  variation  of  serology  which 
shows  a  negative  Wassermann  reaction  in  the  serum,  a  posi- 
tive reaction  in  the  cerebrospinal  fluid,  a  normal  globulin 
reaction,  and  a  pleocytosis  of  from  20  to  50  lymphocytes 
per  c.mm.    This  variety  is  obtained  chiefly  after  treatment, 


138      SEROLOGY   OF  NERVOUS    AND    MENTAL   DISEASES 

and,  as  will  be  shown  later,  presents  a  phase  in  the  methodic 
negativation  of  the  positive  serologic  picture  in  the  course  of 
its  conversion  to  the  "absolutely  negative  type." 

The  serologic  formulae  for  this  form  of  tabes  are  as  follows: 

THE   "ABSOLUTELY   NEGATIVE  TYPE" 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction  of 
Fehling's. 

Negative. 

Negative. 

Normal. 

3  to  8  cells. 

Prompt 
reduction. 

THE   "RELATIVELY   NEGATIVE  TYPE" 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction  op 
Fehling's. 

Negative. 

Negative. 

Normal. 

12  to  32 

cells. 

Prompt 
reduction. 

WASSERMANN   FAST   TABES 

In  speaking  of  those  cases  showing  great  resistance  to 
therapy  I  refer  chiefly  to  the  serology  of  the  serum  and  only 
secondarily  to  that  of  the  cerebrospinal  fluid.  Further  on 
a  suitable  case  will  be  described  to  show  the  permanency  of 
certain  serologic  findings,  and  from  this  it  will  be  seen  that 
the  reverse  of  the  usual  behavior  of  the  entire  serology  takes 
place  as  a  result  of  the  treatment.  A  study  of  the  manner 
in  which  a  serology  of  the  "hyperlymphocytic  type"  becomes 
gradually  "negative"  will  disclose  the  fact  that  the  cells  in 
the  spinal  fluid  are  the  first  to  be  influenced;  the  globulin 
excess  and  the  serum  Wassermann  are  next  affected,  and  be- 
come either  weakly  positive  or  entirely  negative.  This  is 
not  so,  however,  with  the  form  of  tabes  under  discussion. 
Here  the  cells  in  the  fluid,  the  globulin,  and  the  fluid  Wasser- 
mann may  become  entirely  normal,  but  the  positive  serum 
Wassermann  remains  uninfluenced.  It  has  been  main- 
tained that  the  histologic  nucleus  about  which  tabo-paresis 
gradually  develops  may  be  present  for  a  long  time  before 
clinical  manifestations  of  the  coexistent  tabo-paresis  become 
evident.    It  seems  to  me  that  serologic  methods  will  enable 


WASSERMANN    FAST   TABES 


139 


one  to  demonstrate  the  coexistence  of  such  conditions  much 
earlier  than  is  possible  at  times  with  purely  clinical  methods. 
As  examples  of  the  condition  the  following  individual  cases 
are  offered: 

Mr.  S.  P.,  August,  1911,  tabes.     Initial  serology  as  fol- 
lows: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Positive. 

Excess. 

60  lymphocytes. 

Following  this  report  the  patient  was  given  mercury  in- 
unctions, from  2  to  4  gm.  every  third  day.  After  the  ad- 
ministration of  30  inunctions  the  serology  at  the  end  of 
September  was : 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Positive. 

Excess. 

53  lymphocytes. 

After  this  report  the  patient  received  21  intragluteal  in- 
jections of  salicylate  of  mercury,  and  in  December  the 
serology  showed  the  following  improvement: 


Serum  W.  R.             Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Positive. 

Normal. 

50  lymphocytes. 

In  January,  1912,  the  injection  of  a  full  dose  of  salvarsan 
was  given  intravenously.     In  February  the  serology  showed: 

Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Positive. 

Normal. 

41  lymphocytes. 

Since  then,  until  February,  1913,  the  patient  received  five 
intravenous  injections  of  salvarsan,  which  resulted  in  the 
persistence  of  the  positive  Wassermann  in  the  serum,  the 


140      SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 


fluid  Wassermann  became  negative,  and  the  cells  fell  to 
17  per  c.mm. 

It  is  not  essential  for  our  purpose  to  start  with  the  serology 
of  the  "hyperlymphocytic  type";  cases  presenting  an  equally 
strong  resistance  to  treatment  may  be  taken  from  the 
"usual  serologic  type,"  as  the  following  case  will  illustrate: 

Mr.  St.  was  treated  for  three  years  for  a  gastric  catarrh. 
Symptoms  included  Argyll-Robertson  pupils,  absent  knee- 
jerks,  and  subjectively  gastric  crises.  The  serology  per- 
formed in  March,  1911,  showed: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Negative. 

Normal. 

42  lymphocytes. 

Patient  was  given  24  mercury  inunctions,  and  in  May  of 
same  year  showed — 

Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Negative. 

Normal. 

31  lymphocytes. 

June  2d  he  was  given  an  intravenous  injection  of  0.6  gm. 
of  salvarsan,  and  a  serologic  analysis  was  made.  This  showed : 

Sebum  w.  r. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Negative. 

Normal. 

24  lymphocytes. 

The  clinical  course  could  not  be  influenced  by  treatment, 
and  although  the  patient  received  8  more  salvarsan  injec- 
tions intravenously,  the  serum  Wassermann  was  not  affected 
in  the  least. 

The  existence  of  "Wassermann  fast"  tabes  is  strongly 
emphasized  in  the  studies  of  Swift  and  Ellis,  who  use  the  com- 
bined method  of  treatment,  injecting  salvarsan  both  intra- 
venously and  intraspinally.  In  an  article  which  appeared 
in  the  Archives  of  Internal  Medicine,  September  15,  1913, 


WASSERMANN   FAST    TABES 


141 


these  investigators  present  the  results  of  treatment  in 
seven  cases  of  tabes,  in  which  they  used  the  combined 
method.  Of  these  seven  patients,  four  presented  the  "Was- 
sermann  fast"  phenomenon,  in  spite  of  the  vigorous  therapy 
to  which  the  cases  were  subjected.  The  treatment,  as  car- 
ried out  by  these  authors,  is  as  follows: 

Case  213. — O.  W.  A.,  aged  twenty-nine;  syphilis    nine 
years;  tabes,  two  and  one-half  years. 


Date. 

Serum 
W.  R. 

Fluid 
W.  R. 

Globu- 
lin No- 

GUCHI. 

Cells. 

Intra- 
venous, 
Salvar- 

SAN. 

Intraspinous, 
Serum. 

1911 

June  23  to 
Aug.  2... 
Aug.  5  .  .  . 
Aug.  10.  .  . 

to 
Oct.  20.... 
Oct.  27.... 
Nov.  3.... 
Nov.  21... 
Dec.  12 .  .  . 
Dec.  19.  .  . 

1912 
Jan.  5 

+  + 
+  + 

+ 

+ 
+  + 
+  + 
+  + 
+  + 

+ 

0.1± 

0.1  + + 

0.1 +  + 
0.1  +  + 
0.2+  + 

0.1 +  + 

110 

75 

20" 
19 

22 

5x0.2 

4x0.2 
0.2 
0.2 
0.2 
0.2 
0.2 

0.3 

25  c.c.  of  40  per  cent. 

20  c.c.  of  50       " 
30  c.c.  of  70       " 
25  c.c.  of  40       " 

30  c.c.  of  50       " 

From  January  5,  1912,  to  February,  1913,  the  patient 
received  10  salvarsan  injections  intravenously,  each  of  0.3 
c.c,  and,  in  addition,  10  instraspinous  injections  of  30  c.c. 
of  50  and  40  per  cent,  serum.  The  last  analysis  in  February 
showed  a  positive  serum  and  fluid  Wassermann,  no  cells, 
and  a  normal  globulin  reaction. 

Similar  findings  were  had  in  Case  893,  in  whom  10  intra- 
venous and  4  instraspinous  injections  resulted,  at  the  end  of 
six  months,  in  a  ++  serum  Wassermann,  the  fluid  reaction 
being  negative. 

In  Case  152  the  relative  "Wassermann  fast"  condition 
was  obtained.  The  patient  received,  in  the  first  year,  2.2  gm. 
of  salvarsan  in  12  intravenous  injections,  and  then,  in  one 
month,  1.5  gm.  salvarsan  in  5  injections,  plus  3  intraspinous 
injections,  totaling  36  c.c.  of  the  patient's  own  serum.  In 
January,  1913,  the  patient  suffered  a  relapse,  which  was  re- 


142      SEROLOGY   OF   NERVOUS   AND    MENTAL    DISEASES 

lieved  in  two  months  by  giving  7  intravenous  injections  of 
neosalvarsan,  totaling  5.8  gm.,  and  6  intraspinous  injections, 
totaling  72  c.c.  of  the  patient's  serum.  The  resulting  analysis 
in  April,  1913,  gave  a  +=b  serum  Wassermann,  7  cells,  a 
globulin  excess,  and  ±  fluid  Wassermann.  In  this  patient, 
on  one  occasion,  a  negative  serum  Wassermann  was  obtained, 
and  five  times  a  ±  result. 

Case  113  is  another  instance  in  which  salvarsan,  mixed 
treatment,  and  neosalvarsan,  as  well  as  intraspinous  therapy, 
resulted,  after  two  years,  in  the  production  of  a  positive 
Wassermann  in  the  serum. 

In  concluding  the  report  of  the  results  attained  by  them 
from  the  intraspinous  serum  treatment,  the  authors  deplore 
the  fact  that  their  studies  with  general  paresis  were  very 
limited,  not  permitting  them,  at  the  time  this  report  was 
published,  to  formulate  definite  conclusions.  In  one  patient 
with  early  paresis,  and  in  one  or  two  others  who  must  be  con- 
sidered as  border-line  cases  hovering  between  tabes  and 
paresis,  the  treatment  resulted  in  a  rapid  decrease  in  the 
pleocytosis  and  a  moderate  decrease  in  the  globulin,  but 
the  Wassermann  reaction  was  slower  in  showing  a  response 
to  the  treatment. 

The  foregoing  findings  relative  to  the  inability  of  treat- 
ment to  influence  the  Wassermann  reaction  in  some  cases, 
and  the  clinical  opinion  laid  down  as  to  the  possible  transi- 
tion of  tabes  to  general  paresis  is  very  interesting,  more 
especially  regarded  from  the  viewpoint  entertained  by 
myself  throughout  these  analyses. 

Juvenile  Tabes 

This  classification  is  based  on  purely  clinical  findings,  but 
as  the  serology  of  the  serum  and  spinal  fluid  is  often  the 
determining  factor,  it  is  proper  to  consider  it  here.  In  three 
cases  of  this  form  of  locomotor  ataxia  the  serum  was  positive 
in  two,  the  spinal  fluid  Wassermann  was  negative  in  every 
one,  there  was  no  increase  in  the  globulin  content,  and  the 
cell  count  was  43,  35,  and  17  respectively.  The  smaller 
count  was  obtained  in  the  case  that  gave  an  entirely  nega- 
tive result  with  the  other  tests.     In  one  case  the  serologic 


JUVENILE    TABES  143 

investigation  proved  of  great  value  in  making  the  final  diag- 
nosis, as  the  extreme  youth  of  the  patient  almost  made  such 
a  conclusion  impossible.  It  must  nevertheless  be  admitted 
that  infantile  tabes  is  a  possibility,  cases  having  been  de- 
scribed by  Bruce,  Collins,  Maas  and  Hagelstamm,  and  others. 
In  difficult  cases  the  serologic  corroboration  is  an  important 
adjuvant  to  our  methods  of  differential  neurologic  diagnosis, 
particularly  when  one  bears  in  mind  that  such  conditions  as 
pseudotabes  diphtheritica  may  at  times  evince  a  symptom- 
atology closely  simulating  that  of  tabes.  Although  in  this 
disease  the  previous  history  is  frequently  in  itself  sug- 
gestive of  the  cause  of  the  condition,  the  fact  must  not  be 
lost  sight  of  that  diphtheria  may  attack  a  child  with  a 
hereditary  tabes  in  whom  the  cardinal  signs  of  the  spinal 
cord  involvement  prior  to  the  diphtheric  infection  were  not 
sufficiently  severe  to  necessitate  seeking  medical  advice. 

In  such  a  coincidence  the  danger  would  lie  in  placing  too 
much  credence  on  the  history  of  an  infectious  disease  of 
recent  date,  and  omitting  the  lumbar  puncture,  which 
would  settle  at  once  the  real  etiology  of  the  spinal  trouble 
and  indicate  the  proper  line  of  treatment.  The  interpreta- 
tion of  neurologic  disorders  without  the  aid  of  serologic 
methods  will  in  the  future  be  regarded  as  negligence  on  the 
part  of  the  physician,  and  will,  besides,  lead  both  patient  and 
physician  astray.  Surprises  are  always  in  store  for  the 
physician  who  performs  rachicentesis  on  all  neurologic  cases 
as  a  routine  procedure,  and  the  same  applies  also  to  the 
surgeon. 

MONOSYMPTOMATIC    TABES 

The  question  of  the  specific  origin  of  the  fixed  pupil  is  by 
no  means  a  settled  one.  It  cannot  be  denied  that  most  of 
these  pupils  are  of  specific  origin,  and  frequently  constitute 
the  initial  sign  of  tabes.  It  is  not  at  all  uncommon  to  en- 
counter patients  who  present  an  Argyll-Robertson  pupil  and 
yet  have  nothing  else  suggestive  of  tabes.  The  diagnosis 
of  tabes  in  its  incipiency  is  not  always  easy,  particularly 
when  the  spinal  fluid  has  not  been  analyzed.  I  have  in  mind 
three  cases  of  this  form  of  tabes :  in  one,  Mr.  L.,  all  that  could 
be  found  was  a  primary  optic  atrophy;  no  Argyll-Robertson 


144      SEROLOGY    OF   NERVOUS   AND    MENTAL  DISEASES 

pupils;  no  Romberg;  no  Westphal;  no  pain;  no  other  sensory 
disturbances.  Syphilitic  contamination  was  denied,  and 
no  clue  to  the  etiology  of  the  optic  atrophy  could  be  secured. 
The  serology  revealed  the  following  picture: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction  op 
Fehling's. 

Positive. 

Positive. 

Excess. 

160  lympho- 
cytes. 

Prompt. 

From  the  foregoing  serologic  report  there  can  be  no  doubt 
that  syphilis  is  the  cause  of  the  atrophy,  in  spite  of  the  denial 
of  luetic  infection  and  the  absence  of  other  corroborative 
signs  of  lues. 

It  is  quite  evident  that  a  study  of  the  serum  and  fluid  will 
in  some  cases  give  a  clue  as  to  the  etiology;  in  others,  as  to  the 
diagnosis;  and  in  others  again,  as  to  the  line  of  treatment  and 
the  prognosis. 

In  another  case  the  only  symptom  complained  of  was  im- 
potence of  two  years'  duration.  The  difficulty  came  on 
gradually  and  is  now  (1913)  complete.  Patient  denied  syph- 
ilis; has  one  healthy  child.  The  physical  analysis  gave  no 
evidence  suggestive  of  tabes;  reflexes  were  normal,  as  were 
also  the  pupils.  A  band  of  hyperesthesia  was  elicited  in  the 
area  covered  by  the  first  and  second  lumbar  segments.  The 
serologic  analysis  gave  the  following  result: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction  op 
Fehling's. 

Positive. 

Negative. 

Normal. 

67  lympho- 
cytes 

Prompt. 

Here  we  have  the  type  of  serology  that  corresponds  with 
that  obtained  in  the  "usual  serologic  type"  of  tabes.  This 
case  will  be  referred  to  again,  as  the  results  of  treatment  ob- 
tained are  instructive. 

In  a  third  case  the  only  disturbance  complained  of  was  a 
painful  sensation  at  the  head  of  the  penis.    This  was  later 


INFLUENCE    OF   THERAPY    ON    TABES  145 

shown  to  be  a  "penile  crisis,"  and  improved  markedly  after 
treatment.  In  this  instance  the  serology  was  also  positive, 
and  aided  in  the  final  diagnosis  of  the  case. 

The  Influence  of  Therapy  on  the  Serology  and 
Clinical  Course  of  Tabes 

Before  discussing  the  changes  in  the  serology  effected  by 
appropriate  treatment,  it  will  be  well  to  give  suggestions  as 
to  the  advisability  of  therapy  as  may  be  indicated  by  a 
study  of  the  serum  and  the  cerebrospinal  fluid.  All  are  agreed 
on  one  point:  that  the  posterior  spinal  sclerosis  cannot  be 
cured  by  treatment.  Whether  or  not  treatment  can  check 
the  ascending  tendency  of  the  degeneration  has  not  been 
settled.  On  the  other  hand,  it  has  been  quite  well  established 
that  the  inflammatory  processes,  whether  they  be  mild 
or  severe,  can  be  influenced  by  specific  treatment,  and  no 
matter  how  well  chosen  the  remedy,  more  than  this  cannot 
be  accomplished  by  any  means.  Therapy,  therefore,  resolves 
itself  into  a  question  of  who  shall  and  who  shall  not  receive 
the  treatment. 

The  selection  of  patients  suitable  for  treatment  must  be 
made  as  the  result  of  a  thorough  knowledge  of  the  clinical 
and  laboratory  data.  The  active  manifestations  of  tabes 
are,  in  the  majority  of  cases,  due  to  active  processes  in  the 
meninges.  These  are  chiefly  of  an  inflammatory  nature, 
and  frequently  affect  the  cerebrospinal  fluid  in  a  specific 
manner.  This  change  in  the  fluid  is  readily  demonstrated 
by  serologic  methods,  and  will  guide  the  therapeutist  in 
deciding  for  or  against  treatment.  A  purely  degenerative 
tabes,  i.  e.,  a  tabes  devoid  of  any  meningeal  manifestations, 
be  they  ever  so  mild,  is  not  the  rule,  and,  as  previously 
stated,  was  seen  in  only  7  per  cent,  of  the  cases  that  came  to 
the  laboratory  of  the  Institute.  As  was  asserted  elsewhere, 
purely  degenerative  tissue  changes  cannot  be  influenced  by 
treatment,  and  as  the  "negative  type"  of  serology  represents 
the  purely  degenerative  type  of  tabes,  it  is  my  contention  that 
such  tabetics  should  not  receive  the  usual  specific  remedies, 
and  are  better  without  any  treatment.  If  anything  is  to  be 
accomplished,  it  must  be  by  reeducation,  hydrotherapy, 
10 


146      SEROLOGY   OF    NERVOUS    AND   MENTAL   DISEASES 

electricity,  and  not  by  the  introduction  of  substances  that 
are  in  themselves  not  altogether  devoid  of  toxic  properties. 
I  know  of  cases  in  which  the  strenuous  treatment  was  the 
cause  of  the  rapid  decline  of  the  general  health  of  the  patient, 
one  patient  dying  a  few  months  after  treatment  was  insti- 
tuted. The  foregoing  contention  applies  to  the  "absolutely 
negative  type";  the  "relatively  negative  type,"  where  some 
15  to  30  cells  per  c.mm.  are  to  be  found  in  the  spinal  fluid, 
may  be  subjected  to  mild  specific  medication  with  benefit. 
We  will  next  consider  the  effect  of  treatment  on  those 
forms  of  tabes  that  present  serologic  evidence  of  a  menin- 
geal irritation.  First  in  order  is  the  "usual  serologic  type," 
with  a  positive  serum  Wassermann,  a  negative  fluid  Was- 
sermann,  normal  globulin  content,  and  a  cell  count  of  from 
25  to  95  per  c.mm.  The  chief  object  sought  in  the  treat- 
ment of  tabes  is,  of  course,  to  influence  pain  or  other  un- 
plesant  subjective  manifestations.  Besides  this,  it  is  very 
gratifying  to  note  the  improvement  in  the  serologic  picture. 
In  fact,  having  obtained  improvement  subjectively,  it  is  the 
therapeutist's  duty  to  follow  up  the  case  until  the  serology 
has  become  as  nearly  normal  as  it  is  possible  to  make  it. 
That  this  can  be  done  will  be  seen  from  the  following  de- 
scription of  a  case  of  "monosymptomatic  tabes."  We  will 
start  with  the  "usual  serologic  type."  On  November  6, 
1912,  the  serology  was  as  follows: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction  op 
Fehling's. 

Positive. 

Negative. 

Normal. 

67  cells. 

Prompt. 

On  that  day  the  patient  received  an  intravenous  injection 
of  neosalvarsan.  On  November  19th  another  serologic 
studv  revealed: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Positive. 

Negative. 

Normal. 

35  cells. 

INFLUENCE   OF   THERAPY    ON    TABES 


147 


From  November  19th  to  January  7th  three  neosalvarsan 
injections  were  administered,  and  on  December  17th  the 
serology  showed: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Negative. 

Negative. 

Normal. 

21  cells. 

On  the  seventh  of  January,  1913,  the  serologic  report  gave: 

Sebum  W.  R. 

Fluid  W.  R. 

Globulin.                   Pleocytobis. 

Negative. 

Negative. 

Normal. 

0 

Upon  studying  the  changes  obtained  in  the  serum  and 
spinal  fluid  it  will  be  observed  that  the  case  went  through 
a  stage  of  the  "relatively  negative  type,"  and  on  the  seventh 
of  January  showed  the  "absolutely  negative  type"  serology. 
With  the  serologic  negativation  came  the  gradual  return  of 
the  lost  sexual  power,  which  was  preceded,  on  December  28th, 
by  a  disappearance  of  the  band  of  hyperesthesia. 

With  insignificant  variations  in  the  change  from  positive 
to  absolutely  negative  serologic  pictures,  all  other  reports 
follow  approximately  the  same  course.  Regarding  the 
clinical  improvement,  however,  as  much  cannot  be  said, 
as  very  often  the  serologic  picture  becomes  negative  long 
before  the  clinical  exudative  manifestations  have  subsided. 

The  greatest  benefit  to  the  patient,  and  the  source  of  most 
gratification  to  the  physician,  are  to  be  obtained  from  the 
treatment  of  the  "hyperlymphocytic  type"  of  tabes.  This 
type  represents  the  serologic  expression  of  an  exudative  proc- 
ess in  the  meninges,  and  the  presence  of  inflammation  and  of 
syphilis.  The  serology,  as  shown  before,  may  or  may  not  give 
a  positive  Wassermann  reaction  in  the  cerebrospinal  fluid 
(see  Hyperlymphocytic  Tabes),  but  the  chief  index  to  the 
exudative  condition  is  the  high  cell  count.  The  rapidity 
with  which  the  cell  count  in  the  spinal  fluid  falls  after  appro- 
priate treatment  can  almost  be  compared  to  the  diminu- 


148      SEROLOGY   OF    NERVOUS    AND   MENTAL    DISEASES 

tion  in  the  leukocytosis  after  the  opening  of  an  abscess,  and 
the  relief  to  the  patient  is  not  infrequently  as  prompt. 

One  patient  who  suffered  great  pain  and  gave  the  classic 
"hyperlymphocytic  type"  serology  showed  the  following 
picture : 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

PLEOCTTOSI8. 

Positive.               Positive. 

Positive. 

95  ceUs. 

On  January  3,  1913,  the  patient  received  0.9  gm.  of  neo- 
salvarsan  intravenously. 

On  January  20th  the  laboratory  report  gave  the  following 
result : 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Positive. 

Negative. 

73  cells. 

On  January  25th  another  dose  of  neosalvarsan  was  given. 
On  February  9th  the  laboratory  report  showed: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Negative. 

Positive. 

Negative. 

50  ceUs. 

February  10th  patient  received  a  full  dose  of  neosalvarsan. 
February  20th  the  serologic  picture  was: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Negative. 

Negative. 

Negative. 

10  cells. 

In  this  instance  the  clinical  course  was  extremely  grati- 
fying. The  pain  left  the  patient  two  days  after  the  first  in- 
jection, and  did  not  return. 


TABES    AND    GENERAL   PARESES  149 

The  negativation  shown  in  the  preceding  schedules  repre- 
sents the  usual  serologic  findings  in  the  course  of  tabes  fol- 
lowing treatment.  Occasionally  cases  are  encountered  that 
offer  great  resistance  to  treatment,  and  will  not  show  a  nega- 
tive response,  no  matter  how  painstaking  the  therapy.  These 
cases  have  been  considered  under  the  head  of  Wassermann 
Fast  Tabes  (p.  138). 

The  Serologic  Interrelationship  Between  Tabes  and 
General  Paresis 

The  advent  of  a  tabo-paresis  is  frequently  determined 
much  earlier  by  serologic  investigation  than  is  possible  with 
clinical  methods.  The  success  obtained  by  the  reduction  of 
the  pleocytosis  is  counteracted  by  the  inability  to  render  the 
serum  Wassermann  negative.  It  will  be  shown  further  on 
that  the  positive  serum  Wassermann  in  some  cases  of  general 
paresis  closely  simulates  the  serum  of  an  early  case  of  tabo- 
paresis, and  presents,  in  the  majority  of  instances,  a  rela- 
tively insignificant  pleocytosis.  The  two  cases  described 
under  the  head  of  Wassermann  Fast  Tabes  both  developed 
unquestionable  clinical  manifestations  of  tabo-paresis,  the 
first  patient  having  since  died  in  an  insane  asylum  in  a 
paretic  decline.  At  the  time  the  first  serologic  investigation 
was  made  no  clinical  signs  of  paresis  were  demonstrable  in 
either  of  these  patients. 

In  consideration  of  general  paresis  it  should  be  remembered 
that  characteristics  are  to  be  obtained  in  the  serum  from  a 
tabo-paretic  that  will  enable  one  to  classify  certain  sera  as 
suspicious  from  the  very  beginning,  without  subjecting  the 
patient  to  a  prolonged  course  of  treatment.  This  method 
is  not,  however,  to  be  depended  upon  alone,  and  treatment 
is  to  be  applied  to  the  patient  as  a  test  before  the  final  prog- 
nosis can  be  offered  in  a  case  of  tabes.  These  suggestions 
apply  only  to  cases  where  there  is  difficulty  in  the  clinical  in- 
terpretation, where  the  amount  of  treatment  required  by  a 
patient  is  to  be  ascertained,  or  where  it  is  important  to 
render  a  prognosis  in  a  peculiar  case  of  tabes.  It  is  a  gratify- 
ing fact  that  biologic  abnormalities  precede  the  clinical  by 
a  time  interval  sufficiently  great  to  permit  of  therapeutic 


150      SEROLOGY   OF    NERVOUS   AND    MENTAL   DISEASES 

efforts  heroic  enough  to  ward  off  this  disease,  which  is  so 
hopeless  when  once  it  is  apparent  clinically. 

Resume 

Serologically,  tabes  presents  four  distinct  types:  The 
"Usual"  type,  the  "Hyperlymphocytic,"  the  "Negative," 
and  the  "Wassermann  fast"  types.  The  percentage  of  the 
different  types  is  as  follows: 

The  "Usual"  serologic  type 38.0  per  cent. 

The  "Hyperlymphocytic"  type 21.8       " 

f  The  "Negative  type  absolute" 7.0       "\ 

\  The  "Negative  type  relative" 18.6       "  J 

The  "Wassermann  fast"  type 8.5       " 

Miscellaneous  mixed  forms 6.1       " 

Serologic  methods  are  essential  to  the  proper  interpre- 
tation of  the  rarer  forms  of  tabes,  such  as  the  "juvenile" 
and  "monosymptomatic"  forms.  The  "Hyperlymphocytic" 
type  of  tabes,  representing  the  serologic  expression  of 
meningeal  irritation,  is  the  form  of  tabes  most  amenable  to 
treatment.  The  same  holds  true  for  the  "Usual"  serologic 
type. 

Purely  degenerative  processes  do  not,  as  a  rule,  give  the 
findings  commonly  observed  in  exudative  conditions,  hence 
treatment  of  the  "Negative  type"  often  falls  short  of  its 
purpose.  In  a  case  of  tabes  in  which  all  efforts  fail  to  render 
the  serum  Wassermann  negative,  the  advent  of  a  tabo- 
paresis is  to  be  thought  of,  although  at  the  time  no  somatic 
or  psychic  manifestations  may  be  demonstrable.  In  cases 
in  which  treatment  is  beneficial  clinically,  the  result  also 
shows  an  improvement  in  the  serology,  so  that  the  pleocytosis 
tends  to  become  less  pronounced,  the  globulin  excess  disap- 
pears, the  positive  serum  Wassermann  becomes  negative, 
and,  lastly,  the  spinal  fluid  Wassermann  also  becomes  nega- 
tive. In  the  "Wassermann  fast"  type  of  tabes  this  result  is 
not  to  be  attained,  and  if  it  does  occasionally  occur,  a  recur- 
rence is  certain  to  take  place  after  a  short  interval  of  time. 
The  various  serologic  combinations  in  tabes  as  observed  in 
these  studies  were  as  follows: 


RESUME 


151 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

(a)  Positive. 

Positive. 

Excess. 

60  to  96  (63  cases). 

(6)  Positive. 

Negative. 

Excess. 

30  to  88  (54  cases). 

(c)   Positive. 

Negative. 

Normal. 

25  to  95  (162  cases). 

*  (d)  Negative. 

Negative. 

Normal. 

12  to  32    (90  cases). 

(e)   Negative. 

Negative. 

Normal. 

3  to  8     (30  cases). 

(/)   Negative. 

Positive. 

Normal. 

»gg}  (26  cases). 

(g)  Positive. 

Positive. 

Excess. 

The  foregoing  table  includes  all  varieties  observed,  and 
also  takes  into  account  the  treated  and  the  untreated  cases. 
Most  of  the  patients  from  groups  (6)  to  (/)  received  treat- 
ment, and  only  a  few  patients  from  groups  (a)  and  (g)  were 
subjected  to  adequate  therapy  before  the  analyses  were 
made.  The  greatest  number  of  cases  who  presented  the 
"Wassermann  fast"  phenomenon  after  vigorous  therapy 
were  gathered  from  group  (g).  Although  treatment  of  the 
"Negative  type"  offers  little  encouragement  to  the  thera- 
peutist, one  must  bear  in  mind  the  possibility  of  an  exuda- 
tive process  running  its  course  in  a  place  where  the  spinal 
fluid  does  not  actually  come  in  contact  with  the  area  involved, 
and  hence  no  marked  cellular  increase  follows.  This  must 
not  be  lost  sight  of,  particularly  in  those  cases  of  the  "Nega- 
tive type"  of  tabes  that  exhibit  considerable  pain  and  other 
symptoms  showing  involvement  of  the  ganglion  on  the 
posterior  root  (zoster) .  Treatment  of  this  last  form  of  the  dis- 
ease is  often  followed  by  distinct  improvement,  regardless  of 
the  absence  of  a  marked  pleocytosis. 

A  glance  at  the  various  serologic  possibilities  to  be  met 
in  tabes  will  convince  one  that  no  hard-and-fast  rules  can  be 
laid  down  to  enable  one  to  say  beyond  question  that  there 
is  a  combination  of  serologic  findings  that  always  indicates 
the  existence  of  tabes.  Clinical  facts,  collated  with  labora- 
tory findings  as  shown  in  one  complete  picture,  furnish  the 
only  possible  means  for  correctly  diagnosing  a  case  as  tabes. 
Not  infrequently  the  laboratory  is  of  no  assistance  so  far  as 
the  serologic  corroboration  of  tabes  is  concerned,  as  is  the 
case  when  the  "Negative  type"  is  the  form  at  hand.  For- 
tunately, "Negative  types"  and  clinically  obscure  tabes  are 


152      SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 


very  rarely  observed  together,  but  when  they  do  occur,  it  is 
safer  to  defer  the  diagnosis  temporarily.  The  cases  so  far 
considered  that  really  did  offer  clinical  difficulties,  such  as  the 
cases  of  monosymptomatic  tabes  and  the  few  juvenile  forms, 
showed  sufficient  serologic  abnormalities  to  remove  all  doubt- 
as  to  the  genuineness  of  the  tabes. 

In  studying  the  percentages  of  positive  Wassermann  reac- 
tions obtained  in  the  serum  of  patients  with  tabes,  it  will  be 
noted  that  here  and  there  attempts  have  been  made  so  to 
perfect  the  technic,  or  to  introduce  modifications,  as  would 
ultimately  result  in  the  possibility  of  securing  100  per  cent, 
of  positive  Wassermann  reports.  If  this  object  were  really 
attained,  what  laboratory  guide  would  the  therapeutist  have 
for  gaging  his  treatment  or  determining  the  result  of  his  ef- 
forts? There  should  be  sufficient  accuracy  in  the  test  to  give 
a  strong  reaction  with  exudative  tabes,  a  weak  result  when 
the  disease  is  being  properly  treated,  and  a  negative  reac- 
tion at  the  conclusion  of  successful  therapy,  with  the  sole  ex- 
ception of  the  "Wassermann  fast"  type.  All  these  import- 
ant factors  of  the  test  would  be  lost  if  every  tabetic  were, 
from  beginning  to  end,  to  give  a  positive  result  in  his  serum 
or  fluid  with  a  method  incapable  of  error.  Of  course,  an 
unfailing  test  would  be  a  good  thing  where  considerable 
doubt  existed  clinically;  on  the  other  hand,  what  guarantee 
could  we  have  that  the  test  is  infallible?  So  far,  all  the 
modifications  attempted  have  fallen  short  of  their  purpose, 
and  only  tended  to  increase  the  percentage  statistics  of 
syphilis,  and  render  many  an  innocent  sufferer  miserable. 
My  results  in  tabes  gave  the  following  figures: 


Serum  W.  R. 


Fluid  W.  R. 


Globulin. 


Pleocttosis. 


Fehling's 
Reduction. 


Positive,   68 
per  cent. 


Positive,  21 
per  cent. 


Excess,    30 
per  cent. 


Present 
90  per 
cent. 


Present    in 
per  cent. 


100 


CEREBROSPINAL  SYPHILIS 

The  serology  of  this  varied  luetic  involvement  of  the  ner- 
vous system  depends,  first,  upon  the  anatomic  distribution 
of  the  luetic  focus  and  on  its  extent;  second,  upon  the  pecu- 


CEREBROSPINAL   SYPHILIS  153 

liar  tendency  of  the  syphilitic  virus  to  involve,  selectively,  to 
greatest  degree  the  meninges  in  one  patient;  the  inner  walls 
of  the  blood-vessels  in  another,  and  in  a  third,  to  produce 
more  or  less  extensive  tissue  changes  of  a  gummatous  nature. 
Collectively,  these  manifestations  may  be  grouped,  from  the 
clinical  point  of  view,  under  the  head  of  cerebrospinal  syph- 
ilis, or  a  further  classification  of  the  disease  may  be  made 
according  to  its  chief  area  of  distribution — i.  e.,  purely 
cerebral  or  wholly  spinal — regarding  as  cerebrospinal  only 
those  cases  that  present  a  symptom-complex  embracing  both 
anatomic  entities.  From  a  serologic  point  of  view,  it  makes 
considerable  difference  whether  the  disease  is  purely  cerebral 
or  purely  spinal,  and  it  is  still  more  important  to  determine 
whether  the  process  is  a  purely  meningitic,  a  gummatous,  or 
an  endarteritic  one.  The  condition  may  also  be  markedly 
chronic,  and  consequently  present  serologic  differences  be- 
tween this  and  the  acute  form.  In  the  majority  of  instances, 
however,  one  is  forced,  from  the  manner  in  which  the  cerebro- 
spinal fluid  manifests  itself  serologically,  to  conclude  that,  in 
the  great  majority  of  instances,  one  is  dealing  with  a  patho- 
logic state  that  is  closely  allied  to  the  meningitides.  This 
analogy  is  apparent  in  the  absence  in  the  fluid  of  the  Fehling 
reducing  substance,  in  the  presence  of  a  pellicle  in  the  drawn 
fluid,  in  the  great  number  of  cells,  and  in  the  presence  of 
polynuclear  elements.  These  findings,  while  not  the  rule, 
nevertheless  occur,  and  frequently  enough  not  to  be  regarded 
as  exceptional.  In  certain  forms  of  the  disease  these  findings 
are  almost  the  rule,  as  in  the  acute  syphilitic  cerebrospinal 
manifestations.  In  the  gummatous  and  the  endarteritic 
varieties  the  process  is  usually  milder,  and,  of  course,  devoid 
of  the  acute  meningitic  accompaniments. 

Here  and  there  serologic  exceptions  are  encountered,  as 
where  it  is  clinically  demonstrated  that  a  high  cell  count 
ought  to  be  found  and  it  is  not  present,  or  that  the  Wasser- 
mann  reaction  is  negative,  although  the  patient  did  not 
receive  treatment  recently.  These  and  other  similar  findings 
are  mere  coincidences,  which  tend  to  modify  undue  enthu- 
siasm, and  to  render  clinical  evidence  of  greater  value  than 
test-tube  revelations.    On  the  other  hand,  the  clinician  who 


154      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

believes  that  a  neurologic  study  is  incomplete  without  proper 
serologic  investigation  will  be  rewarded  by  finding,  often  to 
his  great  surprise,  that  what  appeared  to  be  a  non-luetic 
disease,  is  unquestionably  cerebrospinal  syphilis.  Such 
incidents  are  not  rare,  and  clinical  impressions  without  an 
accompanying  serologic  report  are  not  infrequently  erro- 
neous, a  result  that  could  have  been  avoided  if  a  laboratory 
had  been  consulted.  It  is  to  be  hoped  that  with  the  routine 
performance  of  serologic  tests  in  connection  with  neurology 
and  psychiatry  the  clinician  will  be  enabled  to  diagnose  and 
treat  his  patient's  malady  more  skilfully  and  successfully. 

In  the  serologic  report  of  a  case  of  cerebrospinal  syphilis 
the  experienced  neurologist,  who  is  accustomed  to  interpret 
such  findings,  discovers  so  much  of  value  from  the  point  of 
diagnosis,  treatment,  and  prognosis,  that  an  omission  of  such 
a  study  would  seem  to  be  more  than  negligence.  As  a 
matter  of  fact,  neurologists  of  experience  do  not  omit  sero- 
logic investigations  any  more  than  they  would  omit  oph- 
thalmologic examinations  and  sensory  charting.  Serology 
has,  as  it  were,  become  an  integral  part  of  a  neurologist's 
armamentarium.  It  is  well  to  emphasize,  at  this  juncture, 
that  to  attempt  to  treat  cerebrospinal  syphilis  without  mak- 
ing routine  serologic  investigations  is  to  deprive  the  thera- 
peutist of  one  of  the  most  exact  and  most  definite  gages  as 
to  the  success  or  failure  of  his  efforts.  This  is  especially 
true  at  the  present  day,  when  we  are  undergoing  a  radical 
change  in  our  therapeutic  conceptions  as  to  the  correct  valua- 
tion of  newly  discovered  drugs,  and  perhaps  are  in  the  forma- 
tive period  of  an  era  that  is  laying  the  foundations  for  the 
establishment  of  an  exact  science— the  treatment  of  syphilitic 
nervous  diseases.  It  is  by  no  means  too  much  to  expect,  in 
the  near  future,  that  a  distinct  therapeutic  formula  will  be 
devised  for  each  and  every  syphilitic  nervous  disease,  based 
on  the  conception  of  the  complete  clinical  entity,  both  bed- 
side and  laboratory. 

The  older  methods  in  vogue  for  the  gaging  of  the  efficiency 
of  a  certain  remedy  necessitated  waiting  for  clinical  improve- 
ment, subjective  and  objective,  to  take  place;  today  this  is 
considered  by  no  means  sufficient,  unless  the  improvement  is 


THE    "POSITIVE    SPINAL   FLUID"    TYPE  155 

accompanied  by  a  corresponding  change  for  the  better  in 
the  serum  and  cerebrospinal  fluid.  The  rapidity  with  which 
the  serologic  picture  of  a  pronounced  cerebrospinal  syphilis 
becomes  almost  normal  is  the  best  guide  as  to  the  efficiency 
of  a  given  method,  and  that  method  which  will  accomplish 
this  in  the  shortest  period  of  time  will  be  the  corner-stone 
for  the  building  of  a  definite  structure  for  the  therapy  of 
syphilis  of  the  nervous  system.  This  work  is  being  carried 
on  in  various  institutions,  and  the  results  are  already  very 
encouraging.  These  results  will  be  dealt  with  more  fully 
in  another  part  of  this  volume. 

The  study  of  cerebrospinal  syphilis,  both  at  home  and 
abroad,  furnished  various  conclusions  from  the  serologic 
point  of  view.  Some  (Hauptmann)  busied  themselves  in 
elaborating  methods,  so  that  not  a  case  of  cerebrospinal  lues 
would  be  overlooked  serologically;  others  (Zeissler,  Kaplan) 
attempted  to  do  quite  the  reverse,  i.  e.,  not  to  stigmatize  one 
with  this  disease  unnecessarily;  others,  again  (Dreyfus, 
Kaplan),  gave  the  serology  of  cases  as  affected  by  therapy. 
Plaut  attempted  to  evolve  a  serology  typical  of  cerebrospinal 
lues  in  contradistinction  to  general  paresis;  a  similar  attempt, 
but  from  a  different  standpoint,  was  made  by  Nonne.  These 
studies  will  be  considered  subsequently,  together  with  the 
similar  findings  as  obtained  by  the  writer. 

THE    "POSITIVE    SPINAL   FLUID"   TYPE 

In  this  form  of  cerebrospinal  lues  the  spinal  fluid  gives  a 
positive  Wassermann  reaction.  The  frequency  with  which 
this  was  observed  by  me  warrants  considering  this  form  of 
serology  of  cerebrospinal  syphilis  under  a  separate  heading. 
Out  of  a  total  of  184  cases  of  lues  cerebrospinalis,  61  gave 
this  serologic  finding,  i.  e.,  33.33  per  cent.  According  to  the 
findings  in  the  fluid,  this  variety  includes  the  most  pro- 
nounced examples  of  syphilitic  cerebrospinal  meningitis,  as 
the  cells  may  be  present  in  such  numbers  as  to  exceed  those 
in  all  the  other  luetic  meningeal  irritations.  This  is  the 
serology  that  Plaut  formerly  held  as  significant  of  general 
paresis;  he  has  since,  however,  altered  his  original  opinion. 
The  conclusions  of  Hauptmann,  on  the  other  hand,  do  not 


156      SEROLOGY    OF    NERVOUS   AND    MENTAL   DISEASES 

admit  of  the  existence  of  the  negative  fluid  Wassermann 
form  ("Plaut  type"  of  cerebrospinal  lues). 

Neither  the  absence  nor  the  presence  of  a  positive  Was- 
sermann in  the  cerebrospinal  fluid  can  serve  as  a  guide  to  the 
diagnosis  or  exclusion  of  general  paresis,  nor  can  the  Haupt- 
mann  experience  be  regarded  as  a  rule  without  exceptions. 

The  Wassermann  reaction  in  the  serum  is  to  a  great  extent 
positive  in  those  cases  that  show  the  higher  cell  counts, — 
100  and  more, — taking  into  consideration  the  possibility  of 
obtaining  a  negative  result  in  a  well-treated  case.  In  the 
untreated  cases  of  this  type  the  reaction  is  present  in  about 
90  per  cent,  of  the  material  as  observed  by  me.  The  posi- 
tive Wassermann  in  the  serum  of  most  cases  is  of  the  same 
degree  of  intensity  as  is  obtained  with  the  usual  serologic 
type  of  tabes.  The  lower  cell  counts  in  cerebrospinal  lues  at 
times  show  a  very  intense  Wassermann  reaction,  not  infre- 
quently simulating  the  "Wassermann  fast"  tabes  serum. 
This  reaction,  however,  does  not  merit  a  special  classifica- 
tion, as  it  does  not  possess  the  clinical  value  of  the  one 
encountered  in  tabes.  Phenomena  are,  however,  encoun- 
tered that  could  be  regarded  as  the  serologic  transition  from 
cerebrospinal  lues  to  general  paresis,  the  serology  not  infre- 
quently being  accompanied  by  clinical  manifestations  of 
beginning  paresis,  of  which  more  will  be  adduced  further  on. 

Certain  prominent  neurologists  believe  that  a  preexisting 
cerebrospinal  syphilis  may  prepare  the  soil  for  the  future 
development  of  paresis.  In  view  of  our  present  development 
of  the  subject  of  neurologic  syphilis,  it  is  almost  impossible 
to  consider  each  of  the  syphilogenous  nervous  disorders  as 
possessing  an  origin  that  is  histologically  entirely  foreign 
to  the  other;  it  is  much  more  logical  to  consider  that  the 
spirochete,  from  the  earliest  involvement  of  the  nervous 
apparatus,  injures  the  structure  in  a  manner  that  is  not  spe- 
cific, in  so  far  as  future  tabes,  cerebrospinal  syphilis,  or  gen- 
eral paresis  is  concerned.  In  one  patient  the  same  organism 
will  produce  tabes;  in  another,  general  paresis;  but  the  be- 
ginning lesion,  from  which  the  clinical  and  pathologic  differ- 
ences arise  in  the  course  of  time,  is  essentially  the  same.  The 
globulin  is  by  no  means  always  in  excess,  and  if  it  is,  this  does 


THE        PLAUT    TYPE 


157 


not  always  show  an  intensity  corresponding  to  the  degree  of 
the  pleocytosis.  We  are  entirely  at  a  loss  at  present  to  ac- 
count for  this  discrepancy,  as  the  factors  that  produce  the 
globulin  excess  are  not  clearly  established.  In  this  form  of 
serology  the  globulin  excess  reached  88.8  per  cent.  The  cell 
count  in  the  untreated  condition,  or  in  cases  in  whom  treat- 
ment was  remote,  ranges  from  100  to  1700  cells.  The  cells 
are  in  the  higher  counts  of  mixed  type,  with  a  large  prepon- 
derance of  the  lymphocytes.  The  polynuclear  elements,  or 
the  polymorphonuclear  cells,  when  present  in  the  fluid 
in  large  numbers, — from  40  to  200  cells  per  cubic  millimeter, — 
also  show  an  absence  of  the  substance  that,  under  ordinary 
circumstances,  reduces  Fehling's  solution. 

These  findings,  taken  together,  justify  the  assumption 
that  a  syphilitic  meningitis  is  at  the  root  of  the  serology,  and 
that  the  cerebrospinal  nervous  system  is  pervaded  by  a  spe- 
cific exudate.  This  exudate  is  most  likely  responsible  for  the 
constriction  of  sensory  nerves  and  pressure  on  motor  tracts 
giving  the  clinical  picture  of  the  disease. 

This  serologic  type  of  cerebrospinal  syphilis  gave  the  fol- 
lowing percentages.  The  figures  show  the  result  of  61 
analyses: 


Serum  W.  R. 


Fluid  W.  R. 


Globulin. 


Pleocytosis. 


Fehling's 
Reduction. 


Positive  55, 
or  90  per 
cent. 


Positive  61, 
or  100  per 
cent. 


Excess  in 
24,  or  40 
per  cent. 


From  160 
to  1800 
per  c.mm. 


Four  fluids  did 
not  reduce,  poly- 
morphonuclears 
up  to  260  per 
c.mm. 


The  absence  of  Fehling's  reducing  substance  is  not  a 
constant  accompaniment  in  cerebrospinal  lues  of  any  type, 
but  when  it  is  absent,  this  is  always  indicative  of  a  very 
active  exudative  process. 


THE    "PLAUT    TYPE' 


This  is  the  negative  spinal  fluid  type,  and  is  the  form  of 
serology  first  described  by  Plant,  comprising  58.2  per  cent, 
of  the  material  analyzed.     This  type  also  represents  the 


158      SEROLOGY    OP   NERVOUS    AND    MENTAL   DISEASES 

intermediary  stage  that  the  positive  type  must  pass  through 
before  becoming  negative  as  a  result  of  treatment.  Despite 
the  fact  that  the  Wassermann  reaction  is  negative,  the 
clinical  intensity  and  the  accompanying  pleocytosis  may  be 
as  pronounced  in  this  as  in  the  "positive  type."  In  discuss- 
ing the  serology  of  tabes  it  was  pointed  out  that  the  serologic 
and  clinical  manifestations  are  not  always  of  the  same  degree 
of  intensity  in  a  patient.  This  holds  true  also  for  cerebro- 
spinal lues.  In  fact,  in  the  study  of  the  fluids  from  patients 
with  this  disease  the  most  astonishing  findings  were  en- 
countered, and  the  serology  in  some  instances  was  the  only 
clue  as  to  the  condition  present.  Diagnoses  that  were  made 
previous  to  the  serologic  analysis  not  infrequently  had  to  be 
reconsidered  after  a  series  of  tests  were  made.  In  six  in- 
stances the  serologic  study  of  the  serum  and  fluid  was  re- 
sponsible for  the  changing  of  the  clinical  diagnosis  from 
general  paresis  to  cerebrospinal  lues,  the  further  course  of 
the  disease  and  its  amenability  to  treatment  tending  to 
confirm  the  latter  diagnosis.  In  one  instance,  that  of  a 
negress  of  twenty-eight  years  who  suddenly  became  ill  nine 
weeks  previous  to  admission  to  the  Institute,  there  were 
very  few  sensory  disturbances,  and  the  reaction  of  de- 
generation was  present;  an  unquestionable  serology  of 
cerebrospinal  syphilis  was  obtained.  The  tentative  clinical 
diagnosis  before  the  laboratory  examination  was  made  was 
anterior  poliomyelitis.  The  Wassermann  reaction  was  posi- 
tive in  the  serum,  and  the  cerebrospinal  fluid  showed  940 
cells  per  c.mm.,  with  many  polynuclear  elements,  a  marked 
excess  of  globulin,  and  an  absence  of  Fehling's  reducing  sub- 
stance. After  this  report  there  was  no  doubt  that  the  patient 
suffered  from  an  acute  exudative  syphilitic  spinal  meningitis. 
Improvement  followed  specific  medication.  These  instances 
emphasize  the  importance  of  performing  the  serologic  tests 
as  a  routine  in  all  neurologic  manifestations. 

Of  the  184  cases  that  furnished  the  material  for  this 
study,  107  presented  the  "Plaut  type"  of  serology.  Eight 
cases  gave  no  reduction  of  Fehling's  solution,  and  also 
showed  the  presence  of  polynuclear  elements.  An  analysis 
of  the  serology  of  this  type  is  as  follows : 


ACELLULAR  TYPE 


159 


Serum  W.  R. 


Positive  in 
94,  or  89.7 
per  cent. 


Fluid  W.  R. 


Negative  in 
107. 


Globulin. 


Excess  in 
66,  or  61 
per  cent. 


Pleocytosis. 


From        96 
to       1400 

cells. 


Reduction  of 
Fehling's. 


Absent    in    8 
fluids,  or  in  7.4 
per  cent. 


ACELLULAR   TYPE 

An  acellular  spinal  fluid  is  rarely  encountered,  but  it 
must,  nevertheless,  be  mentioned,  as  it  illustrates  a  seeming 
incongruity,  and  presents  a  formula  that  is  somewhat  diffi- 
cult to  explain  extemporaneously.  In  the  introductory 
remarks  on  cerebrospinal  syphilis  mention  was  made  of  the 
pathologic  changes  that  the  nervous  system  undergoes  in 
this  disease.  It  was  pointed  out  that  a  meningitic,  a  gum- 
matous, or  an  endarteritic  process  may  involve  the  struc- 
tures. The  acellular  type  is  representative  of  the  endar- 
teritic form,  as  it  is  incapable  of  irritating  the  meningeal 
structure,  as  is  the  case  with  the  gummatous  variety;  nor 
are  the  walls  permeable  to  diapedesis,  as  in  the  meningitic 
form,  so  that  a  condition  is  present  that  is  favorable  to  the 
existence  of  very  few  cells,  regardless  of  the  presence  in  the 
fluid  of  biologic  and  chemical  evidence  of  syphilis. 

It  must  be  borne  in  mind  that  the  serology  is  not  the 
result  of  therapy,  and  does  not  conform  to  the  manner  in 
which  fluids  become  negative  after  having  been  positive. 
The  retrogression  of  the  positive  serology  after  treatment 
does  not  take  place  in  a  haphazard  fashion,  but  follows  more 
or  less  definite  laws,  the  positive  fluid  Wassermann  reac- 
tion becomes  negative  long  before  the  complete  disappear- 
ance of  the  pleocytosis  takes  place.  In  very  few  instances 
have  I  observed  the  contrary,  these  being  chiefly  among 
general  paretics,  where,  after  vigorous  medication,  the  cells 
disappeared  entirely,  leaving  a  positive  fluid  and  serum 
Wassermann  reaction.  The  globulin,  as  a  rule,  is  always  nega- 
tive by  the  time  the  pleocytosis  has  entirely  disappeared. 
The  globulin  excess  without  cells  was  described  when  deal- 
ing with  cord  compression  (tumors,  adhesions,  spinal  caries). 
The  serology  of  the  acellular  type  is,  therefore,  as  follows: 


160      SEROLOGY   OF   NERVOUS    AND    MENTAL  DISEASES 


Sebum  W.  R. 


Positive. 


Fluid  W.  R. 


Positive. 


Globulin. 


Usually 
negative. 


Pleocttosis. 


Reduction  op 
Fehling's. 


Absent     or   Always  prompt, 
borderline. 


As  previously  stated,  this  serologic  form  of  cerebrospinal 
lues  is  very  infrequent,  and  was  observed  in  the  Institute's 
laboratory  in  only  six  patients,  who  gave  no  history  of  recent 
treatment. 


The  Influence  of  Treatment  on  the  Serology  and 
Course  of  the  Disease 

It  may  be  said,  at  the  very  beginning,  that  the  higher  the 
cell  count  and  the  greater  the  number  of  polynuclear  ele- 
ments, the  easier  it  is  to  influence  the  serology  and  alter  the 
clinical  picture  of  cerebrospinal  syphilis  by  proper  treat- 
ment. In  cases  in  which  there  is  an  absence  of  Fehling's 
reducing  substance  the  clinical  result  sometimes  becomes 
evident  on  the  very  next  day,  and  is  closely  followed  by 
serologic  changes  for  the  better. 

This  form  of  lues  cerebrospinalis  will  show  results  after 
any  antiluetic  remedy,  so  far  as  the  serology  is  concerned, 
and  it  is  even  possible  to  obtain  a  diminution  of  cells  in  the 
fluid  simply  by  making  a  lumbar  puncture  and  withdrawing 
some  of  the  fluid,  a  procedure  which  not  infrequently  effects 
an  immediate  amelioration  of  the  patient's  condition;  in 
some  of  these  cases  the  specific  treatment  acts  more  as  a 
prophylactic,  and  gives  the  organic  protective  forces  an 
opportunity  to  relieve  the  exudate.  Subsequently,  when 
the  body  becomes  more  or  less  saturated  by  the  specific  drug, 
the  remedy  will  exercise  its  destructive  properties  on  the 
syphilitic  microorganism,  and  the  opportunities  for  re-forma- 
tion of  the  exudate  are  thus  minimized.  The  destruction  of 
the  spirochetes, — at  least  those  that  may  be  reached  by  the 
drug  through  the  patient's  circulatory  system, — tends  to 
diminish  the  intensity  of  the  Wassermann  reaction  in  the 
spinal  fluid  and  in  the  serum,  which,  when  supplied  in  suf- 
ficient amounts  at  proper  intervals,  may  result  in  a  more  or 


TREATMENT    ON   SEROLOGY   AND    COURSE    OF   DISEASE      161 


less  permanent  negative  serologic  state  and  more  or  less  per- 
manent clinical  cure.  Of  course,  all  that  can  be  done  is  to 
relieve  the  active  manifestations;  organic  tissue  changes  will 
not  be  influenced,  but  will  remain  as  permanent  evidences 
of  the  disease.  When,  however,  the  disease  is  detected  in  its 
very  incipiency,  which,  with  our  modern  methods,  is  not  at 
all  impossible,  the  timely  institution  of  therapy  will  tend 
to  reduce  the  formation  of  permanent  tissue  changes  to  a 
minimum,  and  thus  prevent  a  crippling  of  the  central  ner- 
vous system.  The  "positive  spinal  fluid  type"  and  the 
"Plaut  type"  of  cerebrospinal  lues,  which  show  a  thousand 
or  more  cells  to  the  cubic  millimeter  and  no  reduction  of 
Fehling's  solution,  with  very  few  clinical  manifestations,  are, 
from  a  prognostic  point  of  view,  perhaps  the  most  gratify- 
ing cases  to  treat.  The  following  are  a  few  examples  of  the 
serologic  course  after  specific  treatment: 

Mrs.  H.,  a  Jewess,  aged  forty-two,  housewife.  On  ac- 
count of  low  intellectuality  and  poor  environment  her  mental 
status  offered  analytic  difficulties.  With  the  exception  of 
exaggerated  reflexes  and  a  few  sensory  changes,  no  other 
signs  of  cerebrospinal  lues  existed.  Serology  before  treat- 
ment: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction  of 
Fehling's. 

Strongly 
Positive. 

Positive. 

Excess, 
marked. 

1680  lymph- 
ocytes ; 
260  poly- 
nuclears. 

Absent. 

An  intravenous  injection  of  salvarsan  ("606")  was  given. 
Two  weeks  after  the  injection  another  analysis  showed  the 
following : 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction  op 
Fehling's. 

Positive. 

Positive. 

Mild  ex- 
cess. 

1240  lymph- 
ocytes ; 
20     poly- 
nuclears. 

Present. 

11 


162      SEROLOGY  OF   NERVOUS    AND    MENTAL   DISEASES 

One  week  after  the  serologic  analysis  a  dose  of  salvarsan 
similar  to  the  first  was  administered,  and  the  analysis,  re- 
peated a  week  after  the  second  injection,  showed: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Negative. 

Positive. 

Normal. 

480  lympho- 
cytes. 

Prompt. 

A  third  dose  was  injected  three  days  later,  which  was 
followed  by  a  serologic  analysis  two  weeks  after  the  ad- 
ministration of  the  salvarsan.    This  showed: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Negative. 

Weakly 
positive. 

Normal. 

212  lympho- 
cytes. 

Normal. 

The  mental  change  for  the  better  in  this  patient  was 
marked  after  the  first  injection;  the  reflexes  became  normal 
and  the  sensory  changes  also  disappeared.  The  subsequent 
history  of  the  case  showed  that  no  permanent  injury  to  the 
central  nervous  system  remained  after  the  treatment,  and 
the  patient  is  now  in  perfect  health.  I  believe  that  here 
the  timely  diagnosis  and  treatment  practically  prevented 
permanent  injury  to  the  nervous  apparatus,  first,  by  partly 
evacuating  the  exudate,  and,  second,  by  preventing  its  re- 
formation. 

Mr.  St.,  aged  forty-seven,  married,  no  children.  Com- 
plains of  intercostal  pains;  unable  to  sleep;  poor  memory; 
constipation.  Physical  status,  exaggerated  knee-jerks. 
Irregular  pupils,  sluggish  reaction  to  light.  Serologic  analysis 
gave  the  following: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Positive. 

Negative. 

Positive. 

282  lympho- 
cytes. 

Prompt. 

TREATMENT    ON    SEROLOGY    AND    COURSE    OF   DISEASE      163 


An  intravenous  injection  of  0.6  gm.  of  salvarsan  was  given, 
and  the  serologic  study  repeated  two  weeks  later.  This 
showed : 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Positive. 

Negative. 

Normal. 

174  lympho- 
cytes. 

Prompt. 

Another  injection  was  given  as  before,  and  the  analysis 
on  the  serum  and  fluid,  made  one  week  later,  showed : 

Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Positive. 

Negative. 

Normal. 

88  lympho- 
cytes. 

Prompt. 

A  third  injection  was  given  a  few  days  after  the  serologic 
study,  which  was  followed  by  another  analysis  three  weeks 
later: 


Serum  W.  R.       Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Negative. 

Negative. 

Normal. 

43  lympho- 
cytes. 

Normal. 

This  was  followed  immediately  by  another  injection  as 
before,  and  a  serologic  study  undertaken  one  week  after  the 
last  treatment  showed: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Negative. 

Negative. 

Normal. 

12  lympho- 
cytes. 

Normal. 

The  case  just  described  is  one  of  the  "Plaut  type,"  and  al- 
though it  does  not  present  the  intense  meningitic  phenomena 
that  are  at  times  encountered  in  this  form  of  cerebrospinal 
lues,  it  nevertheless  showed  progressive  improvement  sero- 
logically as  well  as  clinically. 


164      SEROLOGY   OF   NERVOUS   AND    MENTAL   DISEASES 

A  third  case,  originally  diagnosed  as  general  paresis, 
regardless  of  the  laboratory  report  as  to  contrary  serologic 
findings,  was  treated  with  specific  remedies  and  showed  the 
following  progress.     The  serology  before  treatment  was: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Positive. 

Positive. 

Excess. 

148  lympho- 
cytes. 

Prompt. 

Twenty-four  mercuric  inunctions  were  given,  each  of  2 
grams.  The  analysis  made  three  weeks  after  the  cessation 
of  treatment  showed  the  following  changes: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Weakly 
positive. 

Positive. 

Normal. 

1301ympho-| 
cytes. 

Normal. 

After  this  the  patient  made  an  extended  tour,  and  upon 
returning,  three  months  later,  was  given  an  intravenous  in- 
jection of  0.6  gm.  of  salvarsan  intravenously.  A  week  after 
this  the  change  was  as  follows: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Negative. 

Positive. 

Normal. 

92  lympho- 
cytes. 

Normal. 

The  resulting  serology  justified  further  specific  treatment, 
and  the  patient  thereupon  received  a  second  injection  of  sal- 
varsan. Two  weeks  after  this  treatment  the  serologic  in- 
vestigation showed: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Negative. 

Negative. 

Normal. 

19  lympho- 
cytes. 

Normal. 

The  readiness  with  which  the  patient's  serology  responded 
to  the  somewhat  mild  therapy  and  the  clearing  up  of  the 
clinical  manifestations  caused  the  diagnosis  to  be  changed 
from  general  paresis  to  cerebrospinal  lues,  although  the  for- 


TRANSITION  OF  SEROLOGY  OF  CEREBROSPINAL  LUES   165 

mer  diagnosis  was  adhered  to  long  after  the  cessation  of 
active  treatment.  The  improvement  in  this  instance  was  a 
lasting  one.  One  may  say,  however,  that  lucid  intervals 
are  not  uncommon  in  general  paresis;  be  this  as  it  may,  if  we 
can  obtain  a  lucid  interval  for  a  general  paretic  and  prolong 
the  well-being  of  the  patient,  we  certainly  possess  valuable 
measures,  particularly  if  the  serology  can  help  us  in  the  selec- 
tion of  the  cases  that  will  be  most  benefited  by  our  efforts. 

It  must  be  admitted  that,  so  far  as  the  therapy  of  syphilitic 
nervous  diseases  is  concerned,  we  have  not,  as  yet,  passed 
out  of  the  experimental  field,  a  fact  that  is  borne  out  by  the 
new  therapeutic  suggestions  recorded  in  the  medical  press. 
The  possibilities  are  very  encouraging,  and  the  newer  meth- 
ods should  be  employed  where  the  older  ones  have  failed. 
I  am  referring  here  to  the  recent  work  of  Swift  and  Ellis  and 
others,  which  will  be  considered  in  the  section  on  Treatment. 
Although  our  progress  in  the  fields  of  diagnosis,  prognosis, 
and  treatment  has  been  marked,  the  prophylactic  study  of 
syphilitic  nervous  diseases  is  still  virgin  soil.  That  the 
physician  of  the  future — and  let  us  hope  of  the  near  future — 
will  be  able  to  foretell  the  onset  of  a  neurologic  syphilis 
in  a  patient  who  is  in  the  secondary  or  florid  stage  of  the 
disease  is  only  a  question  of  time,  and  therapeutic  measures 
that  will  be  elaborated  for  the  combating  of  neurologic  lues 
will  most  likely  diminish  likewise  the  number  of  tabetics, 
paretics,  and  cerebrospinal  syphilitics.  We  are  almost  on  the 
threshold  of  such  a  possibility.  At  present  all  are  engaged  in 
elaborating  systems  of  therapeutics  that  will,  in  the  short- 
est possible  time,  effect  a  change  for  the  better,  and  tend  to 
make  this  improvement  as  lasting  as  possible.  Some  of  these 
methods  are  far  more  efficient  than  others,  and  are  sure  to 
gain  universal  recognition  sooner  or  later. 

THE  TRANSITION  OF  THE  SEROLOGY  OF  CEREBROSPINAL  LUES 
TO   GENERAL  PARESIS 

The  contention  that  tabes,  cerebral,  spinal,  or  cerebro- 
spinal syphilis,  and  general  paresis,  in  their  very  incipiency, 
cannot  be  distinguished  from  one  another  is  a  fact  that  must 
be  admitted.     It  may  be  said  that  during  the  early  stage 


166      SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

of  its  existence  no  clinical  signs  are  to  be  had  of  any  neuro- 
logic disease,  although  the  soil  for  its  development  is  already 
prepared.  This,  so  to  say,  "aclinical"  lues  of  the  nervous 
system  may,  even  at  so  remote  a  date,  show  serologic  evi- 
dence of  its  existence.  Although  corroborated  by  a  few 
analyses,  it  may,  however,  serve  as  an  interesting  problem 
to  be  solved  by  the  syphilographer,  using  the  latter  term  in 
its  broadest  application,  i.  e.,  one  who  encounters  syphilis 
in  all  its  manifestations,  from  the  initial  lesion  of  the  dis- 
ease to  the  malignant  form  of  skin  syphilis  and  to  the 
paretic  decline.  If  we  assume  that  the  original  impetus  is 
the  same  in  all  neurologic  manifestations  of  syphilis,  it  is 
not  difficult  to  conceive  that  one  clinical  entity  may  be 
transformed  into  another  by  gradual  changes  so  minute  as 
to  go  unobserved  by  the  clinician.  It  is  my  contention  that 
this  imperceptible  clinical  transition  can  be  detected  by 
proper  serologic  studies. 

It  was  mentioned  in  the  section  on  "Wassermann  fast" 
tabes  that  there  the  persistence  of  the  test  was  considered 
as  an  index  to  the  possible  development,  later,  of  a  tabo- 
paresis. In  a  number  of  instances  this  fact  was  established. 
In  regard  to  cerebrospinal  syphilis  or  cerebral  syphilis,  the 
clue  to  the  serologic  transition  stage  is  to  be  found  in  the 
peculiarity  of  the  cell  count  and  in  the  Wassermann  reac- 
tion, and  at  times  also  in  the  globulin  excess.  It  will  be  shown 
later  that  1000  cells  per  c.mm.  is  unknown  in  general  paresis, 
and  that  a  count  of  100  is  not  the  rule  in  cerebrospinal  lues. 
The  cell  count  of  cerebrospinal  lues  is,  as  a  rule,  high;  in  the 
untreated  patient  usually  more  than  100. 

The  therapeutic  guide  is  the  most  certain  differential 
point  between  cerebrospinal  lues  and  the  advent  of  general 
paresis,  the  characteristic  feature  being  a  marked  persistence 
of  all  serologic  abnormalities  in  the  latter.  In  the  attempt 
to  reduce  the  pleocytosis  the  therapeutist  will  discover  that 
no  matter  how  vigorous  the  treatment,  the  cell  count  rarely 
diminishes  below  the  border-line  count,  the  Wassermann 
persists  in  the  serum  or  fluid  or  both,  and  the  globulin  may 
show  a  slight  excess.  Such  a  patient  should  be  closely  ob- 
served for  the  corroborating  clinical  manifestations  of  gen- 


RESUME 


167 


eral  paresis,  as  the  deterioration  is  sure  to  appear  sooner  or 
later.  All  that  can  be  done  in  such  a  state  is  to  employ  all 
means  at  one's  disposal  in  deferring  the  approach  of  the 
much  dreaded  outcome. 

RESUME 

The  material  analyzed  consisted  of  184  cases  of  clinically 
confirmed  lues  cerebrospinalis.    Of  these,  61  gave  the  serology 
of  the  "positive  spinal  fluid  type"  and  107  of  the  "Plaut 
type."    Four  cases  showed  irregular  findings,  and  in  12  the 
serology  was  negative  throughout.     The  latter  were  cases 
that  were  treated  successfully,  the  majority  having  had  one 
of  the  two  positive  serologic  types  before  treatment  was  in- 
stituted.   The  number  of  cases  that  correspond  serologically 
to  the  "Plaut  type"  could  be  materially  diminished  by  em- 
ploying the  "Auswertung's  Methode"  of  Hauptmann,  which 
consists  in  the  use  of  gradually  increasing  quantities  of  cere- 
brospinal fluid  for  the  performance  of  the  Wassermann  test. 
Where  0.2  c.c.  does  not  give  the  reaction,  Hauptmann  ad- 
vises the  use  of  0.4  c.c,  and  so  on  up  to  1  c.c.    In  my  expe- 
rience the  use  of  this  method  did  not  materially  diminish 
the  percentage  of  the  "Plaut  type"  of  cases,  so  that  I  came 
to  the  conclusion  that  this  type  is  a  biologic  reality,  and  is 
not  due  to  the  presence  of  a  diminished  amount  of  antibody, 
which  is  presumably  overcome  by  the  Hauptmann  method. 
In  considering  the  Wassermann  reaction  in  the  serum, 
one  not  infrequently  obtains  a  negative  result  even  when  the 
pleocytosis  is  accompanied  by  polynuclear  elements  and  only 
a  slight  reduction  of  Fehling's  solution,  both  of  which  are 
factors  significant  of  an  active  process  in  the  meninges. 
The  percentage  of  the  various  components  of  the  serology 
of  this  disease  as  found  by  me  is  as  follows:  (a) 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Positive. 

Excess. 

160  to  1680. 

Of  these  61   cases,  which  represent  the   "positive  fluid 
type,"  6  gave  a  weakly  positive  Wassermann  reaction  in  the 


168      SEROLOGY    OF   NERVOUS    AND    MENTAL    DISEASES 

serum,  and  only  24  fluids  gave  the  reaction  of  a  globulin 
excess.  With  these  exceptions  in  mind,  this  type  represents 
about  33  per  cent,  of  the  serologic  findings  in  cerebrospinal 
syphilis. 

(6)  The  "Plaut  type"  gave  the  following  numeric  rela- 
tionship : 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Positive. 

Negative. 

Excess. 

96  to  1240. 

Of  these  107  cases,  13  gave  a  weakly  negative  Wasser- 
mann  reaction  in  the  serum,  and  41  showed  no  globulin 
excess  in  the  spinal  fluid. 

(c)  As  a  result  of  vigorous  treatment,  the  serology  of  12 
cases  showed  the  following: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Negative. 

Negative. 

Normal. 

Normal. 

The  foregoing  shows  that  only  a  very  insignificant  number 
of  cases  result  in  a  restitutio  ad  integrum  so  far  as  the 
serology  in  cerebrospinal  lues  is  concerned;  there  is  no  doubt 
that  with  a  better  knowledge  of  therapeutic  procedure  the 
number  of  such  cases  will  be  sufficiently  increased  to  merit  a 
classification  of  their  own,  and  establish  a  serology  of  the 
successful  post-therapeutic  type.  Each  serologic  item  con- 
sidered independently  and  exclusive  of  the  negative  serology 
obtained  after  treatment  gives,  in  my  experience,  the  fol- 
lowing percentage  relationship: 

Serum  W.  R,.:  Positive  in  88.7  per  cent,  of  cases. 

Fluid  W.  R.:  Positive  in  32.7 

Globulin:  Excess    in  50.3       "  " 

Pleocytosis:  Present  in  96.7       " 

The  question  of  a  pleocytosis  must  without  exception  be 
modified  in  cases  where  an  endarteritic  process  is  the  factor 


RESUME  169 

in  cerebrospinal  syphilis.  Here  a  normal  cell  count  or  a 
borderline  count  will  be  found  with  a  positive  Wassermann 
reaction  in  the  serum  and  fluid,  and  in  half  of  the  cases  a 
globulin  excess.  The  small  number  of  positive  Wassermann 
reactions  in  the  fluid  from  patients  with  this  disease  will  be 
received  with  considerable  reserve  by  those  who  are  ac- 
customed to  work  with  the  "Auswertung's  Methode."  I 
fear  that  the  use  of  too  large  quantities  of  fluid  will  increase 
the  number  of  cases  of  cerebrospinal  syphilis,  so  long  as  such 
a  serology  is  possible  without  the  presence  of  a  pleocytosis, 
as  is  the  case  with  lues  of  the  brain  and  cord  of  the  end- 
arteritic  type.  It  cannot  be  doubted  that  the  real  positive 
fluid  Wassermann  will  inhibit  hemolysis  even  when  used  in 
such  small  quantities  as  0.05  c.c,  and  it  is,  furthermore,  my 
belief  that  only  such  a  spinal  fluid  will  receive  the  same 
interpretation  all  over  the  world. 

In  considering  the  serologic  changes  effected  by  appro- 
priate treatment  it  is  important  to  remember  the  order  of 
serologic  progress  for  the  better;  it  is  very  rarely,  indeed,  that 
the  pleocytosis  disappears  entirely  before  the  Wassermann 
reaction  becomes  negative  in  the  fluid.  Where  opportunity 
is  afforded  for  the  persistence  of  a  positive  Wassermann  reac- 
tion in  the  fluid,  as  is  the  case  where  larger  amounts  of  fluid 
are  used,  a  positive  Wassermann  reaction  will  occasionally 
be  found  where  the  cell  count  has  entirely  disappeared. 
To  have  effected  the  disappearance  of  a  positive  Wassermann 
reaction  from  a  fluid  is  a  considerable  achievement.  If  such 
a  fluid  becomes  negative  after  a  special  method  of  treatment, 
and  the  same  serologic  precautions  in  the  performance  of 
the  test  were  observed  as  before  the  treatment  was  insti- 
tuted, such  therapeutic  procedure  must  be  regarded  with 
favor.  Where  the  Wassermann  reaction  in  the  fluid  is  only 
partly  positive  (after  the  use  of  0.1  or  0.8  c.c),  the  usefulness 
of  the  treatment  is  greatly  diminished  when  the  fluid  be- 
comes negative  after  its  application.  The  performance  of 
serologic  tests  must  be  regarded  as  only  a  small  wheel  in  the 
mechanism  of  clinical  diagnosis,  and  should  never  be  con- 
sidered except  in  conjunction  with  bedside  findings.  Here 
and  there  the  laboratory  diagnosis   will  vary  from  that 


170      SEROLOGY   OF   NERVOUS    AND    MENTAL   DISEASES 

formulated  at  the  bedside,  and  will  occasionally  also  be 
justified  in  taking  exception,  but,  as  a  rule,  both  sides 
agree  in  the  essentials.  Here  and  there  the  serology  will 
give  the  first  clue  as  to  an  impending  general  paresis,  and 
although  the  clinician  will  not  at  the  time  find  sufficient  jus- 
tification for  such  an  assumption,  he  will,  nevertheless,  be  on 
guard  for  the  appearance  of  suggestive  symptoms.  This 
phase  of  serologic  work  is  only  in  its  infancy,  and  as  statistics 
increase  it  will  be  given  wider  consideration. 

The  percentage  of  the  various  serologic  types  of  cerebro- 
spinal syphilis  is  as  scheduled  here: 

The  positive  spinal  fluid  type — 33.1  per  cent. 

The  "Phut  type" — 57.6  per  cent. 

The  acellular  type — 9.3  per  cent.,  inclusive  of  those  cases 
that  became  acellular  after  treatment. 

The  foregoing  also  comprises  a  few  cases  in  which  the  Was- 
sermann  reaction  was  positive  in  the  fluid  and  negative  in 
the  serum. 

Cerebral  Syphilis 

The  purely  cerebral  distribution  of  the  syphilitic  process 
may  manifest  an  acute  or  a  chronic  display  of  symptoms 
and  a  serology  corresponding  to  the  form  of  tissue  change — 
meningitic,  gummatous,  or  endarteritic. 

The  serology  is  greatly  affected  by  the  ease  with  which 
the  spinal  fluid  receives  impressions  from  the  cerebral  fluid. 
If  obstacles  preventing  proper  interchange  exist,  some 
cerebral  luetic  processes  may  entirely  escape  the  serologist. 
In  the  majority  of  instances,  however,  the  meningitic  forms 
give  to  the  fluid  sufficient  distinctive  features  to  suggest 
the  pathologic  condition  at  hand.  The  cerebral  distribu- 
tion of  the  disease  is  entirely  a  matter  of  clinical  differen- 
tiation. 

The  gummatous  form  of  cerebral  syphilis  will  in  so  far 
affect  the  spinal  fluid  as  the  process  is  either  a  superficially 
situated  one  or  one  deeply  embedded  in  the  brain  tissue. 
The  superficially  located  gumma  gives  serologic  changes 
secondarily  only  by  irritating  the  meninges,  so  that  we  are, 
in  reality,  dealing  with  a  mixed  form  of  disease — gummatous 


CEREBRAL   SYPHILIS  171 

and  meningitic.  If  the  process  is  situated  deeply,  the  study 
of  the  cerebrospinal  fluid  will  yield  little  evidence. 

The  purely  endarteritic  form  of  cerebral  lues,  like  the  spinal 
or  cerebrospinal  form,  rarely  gives  a  pleocytosis,  although 
occasionally  a  positive  Wassermann  reaction  may  be  ob- 
tained in  the  fluid. 

From  the  clinical  point  of  view  we  are  dealing  with  the 
hemiplegic  whose  paralysis  is  due  to  a  syphilitic  cerebral 
lesion,  which  may  occasionally  be  obscured  by  intercurrent 
acute  manifestations  of  a  hemorrhagic  nature,  giving  in 
some  instances  the  bloody  fluid  with  red  blood  elements,  in 
other  cases  only  the  dissolved  coloring-matter.  To  this 
class  belongs  the  erythrochromia  of  Mestrezat,  who,  as 
stated  elsewhere,  considers  three  forms  of  xanthochromia. 
The  Wassermann  reaction  varies,  and  the  same  may  be  said 
of  the  globulin  content.  The  other  clinical  form  of  cerebral 
lues  is  evidenced  in  the  patient  with  a  psychosis  who  not  in- 
frequently presents  difficulties  in  the  making  of  a  differential 
diagnosis  between  cerebral  lues  and  general  paresis.  In 
many  instances  definite  symptom  groups  are  sufficient  to 
establish  the  correct  interpretation  of  the  disease;  in  others, 
again,  the  course  of  the  disease  sheds  a  light  on  the  situation, 
but  despite  all  these  differential  aids  at  our  disposal,  we  are 
now  and  then  confronted  by  a  situation  that  does  not  lend 
itself  readily  to  satisfactory  elucidation.  Here  the  serologic 
differentiation  is  at  times  of  great  value,  provided,  of  course, 
that  the  technician  is  also  an  adept  at  interpreting  sero- 
logic findings.  Even  then  the  serology  may  so  closely 
simulate  that  of  general  paresis  that,  in  order  to  establish  a 
correct  diagnosis,  it  would  be  necessary  to  subject  the  patient 
to  a  course  of  treatment  and  then  carefully  note  the  effect 
of  the  same  on  the  serology.  If  the  "Wassermann  fast" 
condition  is  obtained,  we  are  most  likely  dealing  with  a 
general  paresis;  on  the  other  hand,  if  the  Wassermann  reac- 
tion becomes  negative,  it  is  safe  to  consider  the  case  as  one 
of  cerebral  syphilis. 

There  are  cases  on  record  in  which  paresis  existed  for  a  long 
time  without  evincing  the  characteristic  progression  that 
marks  this  disease,  and,  on  the  other  hand,  postmortem 


172      SEROLOGY    OF    NERVOUS    AND   MENTAL   DISEASES 

findings  have  shown  that  luetic  disease  of  the  blood-vessels 
was  present  in  subjects  who  presented  the  symptoms  of 
general  paresis.  In  our  serologic  methods,  I  am  glad  to  say, 
we  have  progressed  a  little  further  regarding  these  confusing 
clinical  entities,  and  where  there  is  doubt  as  to  the  existence 
of  general  paresis,  we  can  frequently  clinch  the  diagnosis  of 
this  disease  if  we  obtain  a  Wassermann  reaction  that  is  "fast," 
a  cell  count  that  is  small,  a  gold  curve  that  is  characteristic, 
and  frequently  also  a  globulin  excess.  If  the  case  were  one 
of  cerebral  syphilis,  the  Wassermann  reaction  would  become 
negative  comparatively  easily  after  therapy;  the  cells,  which 
had  been  present  in  larger  numbers,  would  disappear;  the 
globulin,  if  present,  would  also  become  eliminated,  and 
from  the  beginning  there  would  be  no  characteristic  gold 
chlorid  curve.  All  these  factors,  properly  interpreted,  con- 
stitute to-day  a  valuable  chapter  in  the  clinical  interpreta- 
tion of  syphilitic  nervous  diseases. 

Spinal  Syphilis 

In  this  condition  we  are  now  in  a  position  to  study  the 
cerebrospinal  fluid  as  it  may  be  affected  by  a  local  spinal 
process,  a  condition  easily  detected  by  serologic  methods. 
With  milder  changes  in  endarteritic  luetic  spinal  processes, 
we  find  in  the  meningitic  forms  marked  changes  in  the  cere- 
brospinal fluid.  In  the  gummatous  variety  the  changes  may 
also  be  marked,  but  here  the  fluid  is  not  so  rich  in  cells  as  in 
the  meningitic  variety. 

Here  must  be  considered  the  spinal  pachymeningitis  hy- 
pertrophica  on  a  syphilitic  basis.  The  serology  of  this  form 
is  slightly  different  from  the  other  two  varieties  in  that  the 
globulin  may  at  times  be  present  in  very  great  amounts,  a 
fact  which  may  be  explained  by  the  apparent  similarity 
between  marked  hypertrophic  conditions  that  may  give  rise 
to  considerable  cord  compression,  similar  to  that  produced 
by  cord  tumors.  The  cell  count  is  low,  although  not  so  low 
as  in  the  endarteritic  form.  In  the  meningitic  variety  the 
cell  count  may  reach  into  the  hundreds.  As  to  the  Wasser- 
mann reaction,  the  same  may  be  said  of  the  spinal  as  of  the 
cerebral  form,  in  that  the  reaction  is  present  in  about  half  of 


GENERAL   PARESIS  173 

the  cases  in  the  fluid,  and  to  the  extent  of  about  75  per  cent, 
in  the  serum,  these  figures  not  including  patients  having  re- 
ceived treatment. 

GENERAL  PARESIS 

Of  all  the  luetic  diseases  that  affect  the  nervous  system, 
general  paresis  requires  the  most  care  from  a  diagnostic, 
therapeutic,  and  prognostic  point  of  view.  The  etiologic 
factor  has  been  determined  beyond  doubt  by  Noguchi,  who 
demonstrated  the  Treponema  in  the  brain  tissue  of  paretics. 
The  diagnostic  difficulties,  however,  that  certain  forms  of  this 
disease  offer  in  differentiation  are  by  no  means  removed.  It 
is  hoped  that  with  the  aid  of  serologic  methods  this  much- 
desired  factor  will  to  a  certain  extent  be  attained.  Thera- 
peutically, general  paresis  has  been  the  bugbear  of  those  who 
were  called  upon  to  treat  patients  so  afflicted.  That  serology 
will  point  out  the  form  of  general  paresis  that  is  amenable  to 
treatment,  and  will,  besides,  warn  the  clinician  of  the  im- 
pending advent  of  this  dread  disease,  are  desiderata  likely 
to  be  attained. 

The  involvement  of  the  brain  by  the  Treponema  pallidum 
is  so  peculiar  as  to  make  remedial  agents  of  little  avail  in 
reaching  the  affected  focus.  Deeply  placed  within  the  brain 
tissue,  the  microorganism  propagates,  produces  noxious  sub- 
stances that  call  forth  the  constant  formation  of  specific 
reagines  in  the  body  of  the  host,  a  fact  evidenced  by  the 
strong  positive  Wassermann  reaction.  The  secondary 
meningeal  irritation  is  very  mild,  calling  forth  few  cellular 
elements,  which  must  be  regarded  as  protective  agents.  It 
is  logical  to  expect  that  in  order  to  influence  the  disease,  it  is 
imperative  that  the  infective  agent  be  reached  first.  As  this 
agent  is  very  securely  hidden  in  the  brain  tissue,  rather  re- 
mote from  vascular  channels,  it  is  clear  that  more  strenuous 
methods  must  be  employed  in  order  to  check  the  further 
propagation  as  well  as  the  concomitant  formation  of  toxins 
by  the  treponema.  Hence  the  difficulty  encountered  up  to 
the  present  time  in  checking  the  disease  by  ordinary  thera- 
peutic measures,  such  as  are  usually  employed  with  more  or 
less  success  in  cerebrospinal  lues  and  in  exudative  tabes. 


174      SEROLOGY    OF   NERVOUS   AND    MENTAL   DISEASES 

It  is  small  wonder  that  the  prognosis  from  a  therapeutic 
outlook  in  these  cases  was  very  pessimistic.  The  reason 
for  the  failures  is  to  be  found  in  the  fact  that  the  remedial 
agent  did  not  reach  the  microorganisms,  or  that  when  it 
came  in  contact  with  them  it  was  too  weak  to  destroy  the 
virus  entirely,  but  permitted  sufficient  numbers  of  the 
infecting  microorganisms  to  survive  to  give  rise  to  the 
propagation  of  a  new  generation  of  treponemse.  As  the 
result  of  the  many  failures  that  attended  such  efforts,  they 
are  rapidly  becoming  obsolete  in  the  treatment  of  this  dis- 
ease. 

The  outlook  at  present  for  the  successful  treatment  of  act- 
ive syphilis  of  the  central  nervous  system  is  very  bright;  in 
fact,  good  results  are  already  attained  in  the  active  manifes- 
tations of  tabes,  the  patient  being  relieved  of  the  pains  in  a 
manner  that  is  remarkable.  These  data  covering  this  part 
of  the  therapy  will  be  considered  in  the  section  on  Salvarsan 
and  its  Administration. 

The  Distribution   of  the  Treponema   Pallidum  and 
its  Detection 

The  distribution  of  the  Treponema  pallidum,  to  quote 
Noguchi,  is  to  the  gyrus  rectus,  frontalis,  Rolandic  area, 
and  in  some  instances  to  the  gyrus  hippocampi  and  in 
Ammon's  horn.  The  microorganisms  are  found  in  greater 
numbers  in  the  cortical  layers,  and  to  a  less  extent  in  the 
nerve-fiber  zone. 

If  the  sections  are  properly  counterstained  with  toluidin 
blue  or  thionin,  it  can  be  seen  that  a  pyramidal  cell  is  closely 
surrounded  by  one  or  more  organisms,  and  in  some  instances 
are  inserted  even  into  the  cytoplasm  of  the  cell.  An  amor- 
phous precipitate  may  be  visible  in  the  vicinity  of  some  of  the 
pyramidal  cells;  this  Noguchi  believes  to  be  an  exudate. 
These  pyramidal  cells  show  degenerative  changes,  as  is 
evidenced  by  their  altered  contour,  by  swelling,  and  by  the 
disappearance  of  their  nuclei.  The  Treponema  pallidum  is 
very  rarely  found  in  the  vicinity  of  blood-vessels,  and  al- 
most never  within  the  vessel-wall.  Noguchi  is  not  certain 
that  he  encountered  the  microorganism  in  the  pia. 


«   1  J 


*- 


'  3 


Fig.  19. — Showing  Treponema  pallidum  (A)  in  the  cortex  of  a  patient 
who  died  of  general  paresis  during  a  seizure.  Stained  by  a  modified 
Levaditi.    Magnification  1100.     (Courtesy  of  Dr.  H.  Noguchi.) 


TECHNIC   OF    TISSUE    STAINING  175 

Although  the  technic  of  preparing  tissue  and  sections  for 
the  study  of  the  organism  under  consideration  is  not  a  sero- 
logic subject,  it  is  so  important  that  the  author  considers  it 
necessary  to  describe  the  procedure  in  detail. 

TECHNIC    OF  TISSUE    STAINING 

It  is  of  the  greatest  importance  that  the  tissue  be  com- 
pletely fixed  prior  to  impregnation.  Specimens  fixed  for  a 
year  give  excellent  results. 

Sections  from  one  or  more  of  the  areas  previously  men- 
tioned, and  which  have  been  hardened  in  10  per  cent,  forma- 
lin, a  slice  of  material  measuring  from  5  to  7  mm.  in  thick- 
ness, and  being  of  variable  dimensions  otherwise,  is  put  into 
a  mixture  consisting  of  10  per  cent,  formalin,  10  per  cent, 
pyridin,  25  per  cent,  acetone,  25  per  cent,  alcohol,  and  30  per 
cent,  distilled  water.  The  tissue  is  allowed  to  remain  in  this 
for  five  days  at  room  temperature.  It  is  then  thoroughly 
washed  in  distilled  water  for  twenty-four  hours.  It  is  next 
transferred  to  96  per  cent,  alcohol  for  three  days,  and  again 
thoroughly  washed  with  distilled  water  for  twenty-four 
hours.  After  this  the  specimens  are  placed  in  a  dark  bottle, 
and  receive  the  following  treatment: 

1.  In  1.5  per  cent,  silver  nitrate  solution  for  three  days  at 
37°  C.  (or  five  days  at  room  temperature). 

2.  Wash  in  distilled  water  for  several  hours. 

3.  Reduce  in  4  per  cent,  pyrogallic  solution,  with  the 
addition  of  5  per  cent,  formalin  for  twenty-four  hours  at 
room  temperature. 

4.  Wash  thoroughly  in  distilled  water. 

5.  Transfer  to  80  per  cent,  alcohol  for  three  days. 

6.  Then  transfer  to  95  per  cent,  alcohol. 

7.  Place  in  absolute  alcohol  for  two  days. 

8.  Xylol,  paraffin-xylol,  paraffin. 

The  tissue  is  now  ready  for  sectioning,  the  thickness  of 
the  section  depending  upon  the  degree  of  impregnation,  and 
varying  with  different  specimens  of  the  brain.  As  a  rule  they 
are  cut  3  micra  thick,  but  when  5  micra  in  thickness  the 
chances  for  finding  more  numerous  specimens  are  increased. 


176    serology  of  nervous  and  mental  diseases 

The  Theory  of  the  "Wassermann  Fast"  Phenomenon 

The  serologic  abnormity  that  first  draws  the  attention  of 
the  laboratory  worker  to  the  initiation  of  a  change  suggestive 
of  the  onset  of  general  paresis  is,  theoretically  speaking,  con- 
temporaneous with  the  embedding  of  the  treponemas  in  the 
brain  tissue  proper,  having  migrated  by  gradual  stages  from 
the  meninges.  The  resulting  serum  analyses  are,  therefore, 
persistently  positive,  and  remain  so,  in  the  majority  of  cases, 
regardless  of  the  treatment  usually  administered.  This  is 
most  likely  the  condition  of  affairs  that  exists  in  the  "Was- 
sermann  fast"  tabes,  which,  in  my  experience,  is  the  serologic 
precursor  of  a  taboparesis.  It  cannot  be  regarded  as  erro- 
neous to  consider  cerebrospinal  lues,  tabes,  and  general 
paresis  as  originally  one  disease,  each  exhibiting  different 
peculiarities  of  distribution  of  the  microorganisms.  It  is 
also  possible  that  a  predisposition  on  the  part  of  the  indi- 
vidual infected  plays  a  role  in  the  production  of  the  particu- 
lar form  of  nervous  yphilis,  and  the  possible  existence  of 
more  than  one  variety  of  treponema  capable  of  producing 
lues  must  also  be  considered. 

The  general  distribution  in  cerebrospinal  syphilis  speaks 
for  the  invasion  of  the  meninges  by  the  organisms;  in  general 
paresis,  again,  the  organisms  are  more  deeply  placed;  in  the 
former  disease  the  Wassermann  reaction  is  rendered  "negative 
with  comparative  ease,  the  virus  still  being  intravascular; 
in  the  latter  the  virus  is  protected  by  a  wall  of  brain  tissue. 

If  it  were  possible  to  attack  the  Treponema  pallidum  at 
the  time  when  it  begins  to  change  its  abode,  or  if  tests  could 
be  devised  for  the  detection  of  this  more  or  less  fatal  transi- 
tion, then  we  would  possess  a  means  of  warding  off  the  paretic 
attack.  That  a  preexisting  cerebrospinal  lues  in  some 
patients  paves  the  way  for  the  future  development  of  general 
paresis  was  a  theory  advanced  by  Charles  L.  Dana  years 
ago,  and  it  became  incumbent  on  the  serologist  to  furnish 
a  reaction  or  a  number  of  reactions  capable  of  directing  the 
clinician's  attention  to  the  fact  that  the  dangerous  transition 
was  at  hand. 

Although  not  established  on  an  absolutely  sure  foundation, 


THEORY    OF    '*  WASSERMANN    FAST  "    PHENOMENON      177 

it  would  seem  that  in  *the  behavior  of  the  Wassermann  reac- 
tion, the  globulin  test,  and  the  pleocytosis  we  have  an 
index  as  to  the  possible  onset  of  general  paresis  in  a  patient 
that  may  have  been,  and  even  yet  is,  afflicted  with  cerebro- 
spinal lues.  This  question  was  touched  upon  in  the  con- 
sideration of  cerebrospinal  syphilis,  and  is  to  be  elaborated 
here  more  extensively. 

Before  giving  the  serology  of  typical  general  paresis,  the 
author  wishes  to  emphasize  the  fact  that  the  positive  Was- 
sermann reaction  in  this  disease  is  somewhat  different  from 
the  positive  Wassermann  result  obtained  in  other  syphilitic 
nervous  diseases,  unless  they  are  undergoing  a  transition 
stage  to  general  paresis.  As  is  well  known,  the  second  part 
of  the  Wassermann  reaction  consists  in  the  hemolytic  incu- 
bation. The  test-tubes  containing  syphilitic  sera  will  begin 
to  show  a  clear  zone  at  the  top  of  the  tube,  the  cells  gradually 
sinking  to  the  bottom.  The  time  required  for  this  phe- 
nomenon to  manifest  itself  is  from  ten  to  thirty  minutes. 
Those  who  are  accustomed  to  read  Wassermann  end-results 
will  note  that  the  sinking  of  the  cells  to  the  bottom  takes 
place  much  sooner  in  some  tubes  than  in  others;  in  some 
cases  this  may  consume  even  one  hour  or  more.  The  tubes 
that  show  this  early  sedimentation  are,  as  aTule,  those  con- 
taining sera  from  "patients  with  general  paresis.  If  the  test- 
tube  racks  are  gently  removed  from  the  incubator  without 
the  least  shaking  of  the  tube  contents,  it  will  be  observed 
that  the  sera  of  general  paretics  show  a  lateral  constric- 
tion, similar  in  conformation  *to  two  parenthesis  signs 
placed  with  their  convexities  toward  each  other, — )(, — the 
sides  being  entirely  clear,  and  the  top  and  bottom  fluids 
being  opaque  and  of  an  old-rose  color.  Not  the  slightest 
trace  of  free  hemoglobin  is  to  be  detected  in  the  fluid  after 
twenty-four  hours'  standing,  the  supernatant  liquid  being 
of  the  transparency  and  color  of  clear  water.  In  the  vast 
majority  of  instances  this  will  be  the  case  when  the  serum 
is  that  from  a  patient  with  general  paresis.  It  was  pre- 
viously emphasized  that  the  cell  count  in  cerebrospinal 
syphilis  numbers,  as  a  rule,  over  100  cells  per  c.mm.;  later 
we  shall  see  that  the  pleocytosis  in  general  paresis  is  only 
12 


178      SEROLOGY   OF   NERVOUS    AND    MENTAL   DISEASES 

very  exceptionally  above  100,  and  presents,  in  the  majority 
of  instances,  less  than  60  cells  per  c.mm. 

In  the  course  of  treatment  of  a  case  of  lues  cerebrospinalis 
the  serologic  return  to  a  more  or  less  normal  state  follows 
certain  well-defined  paths,  unless  the  patient  shows  a  tend- 
ency toward  the  development  of  general  paresis.  This 
tendency  is  manifested  by  a  marked  fall  in  the  cell 
count  as  a  result  of  the  treatment,  but  the  Wassermann 
reaction  remains  uninfluenced.  When  the  Wassermann 
reaction  persists,  and  besides  shows  the  peculiarity  pre- 
viously spoken  of,  the  serologic  evidence  that  the  transition 
from  cerebrospinal  lues  to  general  paresis  is  about  to  take 
place  is  at  hand.  The  persistence  may  be  either  in  the 
serum  or  fluid,  and  the  latter  may  or  may  not  show  the 
reaction  of  a  globulin  excess.  These  serologic  manifesta- 
tions need  not  go  hand  in  hand  with  the  clinical  evidences; 
on  the  contrary,  many  months  may  elapse  before  clinical 
corroboration  establishing  the  justice  of  the  laboratory's 
contention  can  be  adduced.  In  one  instance  that  came  to 
the  author's  notice  the  paretic  manifestations  became 
apparent  three  years  after  the  opinion  had  been  advanced 
by  the  serologist. 

The  early  recognition  of  the  transitory  stage,  if  it  may 
be  so  termed,  is  much  more  important  now  than  it  was 
before  the  era  of  modern  therapeutics,  for  the  reason  that 
it  is  sometimes  possible,  with  the  proper  use  of  newer  reme- 
dial agents,  to  check  the  further  advance  of  the  disease. 

The  "Serology  of  the  Full-fledged  Type 

Under  this  head  are  included  those  cases  that  gave  clinical 
evidence  of  the  existence  of  paresis  and  some  in  whom  the 
diagnosis  was  made  only  after  the  serologic  report  had  been 
presented.  Before  the  serology  was  submitted  in  these  cases 
the  diagnosis  rested  between  cerebrospinal  lues,  cerebral 
syphilis,  and  arteriosclerosis. 

This  type  of  serology  was  encountered  in  120  out  of  261 
cases  of  general  paresis,  and  presented  all  the  serologic  char- 
acteristics mentioned  in  the  introductory  remarks.  The 
findings  were  as  follows : 


OTHER    SEROLOGIC   COMBINATIONS 


179 


Serum  W.  R.       Fluid  W.  R. 


Positive.         Positive. 


Globulin,     i  Pleocttosis. 


Excess. 


17  to  50. 


Reduction. 


Prompt. 


The  pleocytosis  of  this  type,  together  with  the  intensely 
positive  Wassermann  reaction  and  the  globulin  excess,  is 
typical  of  the  condition.  On  very  rare  occasions  only  is  this 
picture  present  in  a  case  of  tabes,  and  when  such  is  the 
case,  it  becomes  the  physician's  duty  to  employ  strenuous 
methods  to  overcome  this  type  of  serology,  as  it  means,  very 
often,  a  tendency  toward  the  development  of  a  general 
paresis. 

Other  Serologic  Combinations 

In  a  number  of  patients,  63  in  all,  the  cell  count  ranged 
from  62  to  78  per  c.mm.  Some  of  these  patients  received 
vigorous  treatment  and  showed  some  improvement  as  a 
result.  In  29  others  the  serology  was  somewhat  different, 
and  may  for  the  time  be  considered  as  of  a  type  that  is  less 
pernicious  than  is  the  full-fledged  type  just  considered. 


Serum  W.  R.      Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Positive,     j    Negative. 

Excess. 

65  to  80. 

Prompt. 

The  serology  here  outlined  resembles  slightly  that  which 
one  might  expect  to  find  in  a  case  of  cerebrospinal  syphilis  of 
the  Plaut  type  after  a  course  of  treatment.  It  is  more  often 
the  case,  however,  that  during  the  course  of  treatment  the 
serum  Wassermann  becomes  negative  before  the  fluid  Was- 
sermann reaction,  particularly  when  the  cells  in  the  fluid 
show  a  marked  reduction  in  numbers.  In  addition  to  the 
apparent  resemblance  of  the  serology  of  cerebrospinal 
syphilis  to  the  Plaut  type,  the  French  school  (Marie)  be- 
lieves that  the  very  incipiency  of  the  paretic  serology  mani- 
fests itself  in  a  picture  analogous  to  that  of  the  29  cases 
above  cited,  i.  e.,  the  serum  is  positive  and  the  fluid  nega- 
tive. The  French,  however,  do  not  consider  that  the  upper 
limit  of  the  pleocytosis  is   also   of    significance,   a    point 


180      SEROLOGY    OF    NERVOUS   AND    MENTAL   DISEASES 

that  must  be  remembered  in  determining  the  logical  con- 
struction of  a  transitory  serology  from  the  one  disease  to  the 
other.  This  French  opinion  will  be  dwelt  on  more  fully 
further  on.  It  should  be  borne  in  mind  that  the  negative 
Wassermann  reaction  in  a  patient's  cerebrospinal  fluid  with 
clinical  evidence  of  general  paresis  removes  it,  so  far  as  the 
serologic  interpretation  is  concerned,  from  the  full-fledged 
type  of  the  disease.  Even  if  the  French  teaching  is  true  only 
in  part,  it  nevertheless  holds  out  some  hope  to  the  paretic 
who  presents  the  so-called  early  type  serology,  which  may 
be  regarded,  following  Dana's  reasoning,  as  the  transition 
from  a  cerebrospinal  syphilis.  This  form  of  serology  may, 
therefore,  be  considered  as  favorable  for  the  employment 
of  therapeutic  measures,  a  contention  that  was  corrobo- 
rated by  the  improvement  that  followed  treatment  of  cases 
presenting  this  type  of  serology.  The  developments  in  the 
treatment  of  nervous  diseases  of  syphilitic  origin  are  so 
promising  at  the  present  time  that  great  hope  is  entertained 
as  to  the  ability,  in  the  future,  of  warding  off  indefinitely 
the  fatal  paretic  deterioration.  Of  this,  more  will  be  ad- 
duced in  the  section  on  Salvarsan  and  its  Administration. 

The  attitude  of  Plaut,  in  his  book  on  "The  Wassermann 
Sero-diagnosis  of  Syphilis  in  its  Application  to  Psychiatry," 
is  very  significant  in  connection  with  the  stand  taken  by  the 
author.  On  page  86  of  the  American  translation  of  1911 
Plaut  is  quoted  as  saying  that  one  does  not  go  too  far  in 
accepting  as  true  the  statement  that  paretics,  at  the  time 
of  onset  of  the  disease,  are  still  syphilitics;  these  conclusions 
being  based  on  the  fact  that  in  so  far  as  the  intensity  of  the 
Wassermann  reaction  is  concerned  in  the  serum,  these 
patients  manifest  the  same  symptoms  as  patients  in  the 
florid  stage  of  syphilis,  and  differ  clearly  from  those  in  the 
latent  tertiary  stage.  The  phrase  "at  the  time  of  onset" 
is  very  significant,  at  least  it  appears  so  to  the  author,  for 
it  is  at  this  time  that  the  Wassermann  reaction  is  very 
strongly  positive  in  the  serum,  and  may  not  show  a  positive 
result  in  the  cerebrospinal  fluid  at  all — a  fact  that  links 
more  closely  together  the  interrelationship  of  the  serology  of 
general  paresis  and  cerebrospinal  syphilis,  particularly  the 


OTHER   SEROLOGIC    COMBINATIONS 


181 


type  described  by  Plaut.  Besides  the  type  of  serology  that 
gives  a  negative  Wassermann  reaction  in  the  cerebrospinal 
fluid  there  is  another  that,  similarly,  does  not  show  a  globulin 
excess,  as  may  be  seen  from  the  following  table: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Positive. 

Negative. 

Negative. 

30  to  83. 

Prompt. 

This  serology  was  obtained  in  25  cases,  and  it  was  deemed 
better  to  consider  two  patients  as  in  the  transition  stage 
from  cerebrospinal  syphilis  to  general  paresis.  These  two 
cases  showed  81  and  83  lymphocytes  respectively,  and 
reacted  very  favorably,  both  clinically  and  serologically,  to 
treatment.  The  cell  count  diminished  markedly,  the  Was- 
sermann reaction  became  negative  after  three  months  of 
therapy,  and  the  patients  were  able  to  resume  their  vocations, 
reporting  regularly  every  three  months  for  serologic  analysis. 

Another  combination  of  serologic  findings  must  be  re- 
ported, as  these  cases  exemplify  the  French  type  of  the 
advanced  disease: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Reduction. 

Negative. 

Positive. 

Positive. 

15  to  29. 

Prompt. 

This  serologic  study  disproves  the  contention  that  general 
paresis  always  gives  a  positive  serum  Wassermann  reaction. 
This  form  of  serology  most  frequently  occurs  in  the  later 
stages  of  the  disease,  and  is  encountered  most  often  during 
the  paretic  decline,  in  patients  who  are  afflicted  with  bed- 
sores and  whose  mentality  is  entirely  shattered. 

Plaut  observed  eight  cases  with  very  slight  pleocytosis  and 
a  serology  similar  to  that  described  among  the  serum  nega- 
tive findings  elsewhere.  In  the  author's  experience  only 
14  such  serologic  findings  were  obtained,  but  Plaut's  series 
is  introduced  here  chiefly  to  point  out  his  contention 
that  5  out  of  his  8  patients  were,  in  his  opinion,  cases  of 
beginning  paresis;  on  the  other  hand,   the   same  worker 


182      SEROLOGY    OF    NERVOUS    AND   MENTAL   DISEASES 

describes  one  of  the  cases  that  at  autopsy  proved  to  be  an 
ordinary  case  of  advanced  paresis.  Later  he  makes  the  as- 
sertion that  he  has  observed  enough  cases  of  beginning 
paresis  with  a  very  decided  cellular  increase.  This  latter 
view  is  entirely  in  accord  with  our  findings  at  the  Institute, 
i.  e.,  that  a  decided  pleocytosis  marks  the  early  paretic;  a 
slight  pleocytosis  and  a  negative  serum  Wassermann,  on 
the  other  hand,  in  the  majority  of  instances  are  significant 
of  the  advanced  form.  The  full-fledged  type  expresses  the 
serology  of  the  fully  developed  form  of  the  disease  as  found 
in  the  greater  number  of  cases.  The  last  form  of  serology 
to  be  described  will  seem  almost  an  impossibility  to  those  who 
have  worked  with  serologic  methods  that  tend  to  make 
the  Wasserman  reaction  more  sensitive,  as  the  findings  are 
entirely  negative: 


Serum  W.  R. 

Fluid  W.  R. 

Globule*. 

Pleocytosis. 

Reduction. 

Negative. 

Negative. 

Normal. 

5  to  11. 

Prompt. 

A  computation  of  the  percentage  of  the  various  serologic 
posibilities  will  show  that  this  form  is  the  one  least  likely  to 
occur,  and  the  10  cases  collected  that  presented  this  serology 
include  3  who  received  very  strenuous  treatment,  each 
having  had  over  18  intravenous  injections  of  salvarsan. 
These  patients  improved  after  the  first  ten  to  twelve  injec- 
tions, so  that  it  was  thought  advisable  to  push  the  treatment 
until  the  serology  would  become  negative.  The  foregoing 
findings  show  the  result  of  the  treatment,  these  being  prac- 
tically normal.  The  serology  of  the  remaining  7  does  not 
give  any  particular  evidence,  but  serves  to  emphasize  the 
previous  contention  that  one  is  not  justified  in  making  rules 
that  are  hard  and  fast  and  that  permit  of  no  exceptions. 
There  is  only  one  uncontrovertible  rule,  and  that  is  that  a 
positive  serology  is  not  compatible  with  a  nervous  disease 
of  non-luetic  origin;  on  the  other  hand,  a  negative  serology 
may  be  obtained  in  a  syphilitic  nervous  disease.  In  general 
paresis  the  various  serologic  combinations  showed  the  fol- 
lowing proportions : 


FRENCH  CONCEPTION  OF  SEROLOGIC  PROGRESSION   183 


Serum  W.  R. . 

Positive. 

Positive. 

Positive. 

Negative. 

Negative. 

Fluid  W.  R... 

Positive. 

Negative. 

Negative. 

Positive. 

Negative. 

Excess. 

Excess. 

Normal. 

Excess. 

Normal. 

Pleocytosis  . 
Reduction..  . 

17  to  50. 

62  to  78. 

65  to  80. 

30  to  83. 

15  to  29. 

5  to  11. 

Prompt. 

Prompt. 

Prompt. 

Prompt. 

Prompt. 

Prompt. 
10  cases, 

63  cases, 

29  cases, 

25  cases, 

14  cases, 

or  24 

or  11 

or  9.5 

or  5.3 

or  3.8 

per  cent. 

per  cent. 

per  cent. 

per  cent. 

per  cent. 

per  cent. 

The  French  Conception  of  Serologic  Progression 

Marie  and  his  pupils  formulated  a  series  of  reactions  as 
exhibited  by  the  disease  in  its  various  stages.  These  workers 
obtained  different  serologic  results  in  the  beginning^  of  the 
disease,  these  differing  also  from  the  analyses  obtained  in 
cases  in  which  the  disease  was  fully  developed  and  during 
its  decline.  Although  other  workers,  including  the  author, 
could  not  corroborate  Marie's  finding  in  every  instance, 
it  must  nevertheless  be  accepted  as  an  established  fact, 
although  in  some  instances  contrary  results  were  obtained. 
Of  the  patients  whose  serology  is  shown  in  the  foregoing 
table,  some  of  the  29  in  the  third  column  were  in  a  moribund 
condition,  and  one  of  the  14  in  the  fifth  group  showed  clinical 
signs  of  the  very  earliest  advent  of  the  disease.  The  facts 
taken  together,  making  allowance  for  exceptions  that  all 
laboratory  data  are  entitled  to,  present  a  guide  that  can  be 
accepted  for  occasional  use  in  the  classification  of  the  stage 
of  the  disease.  Discrepancies  will  naturally  be  encountered, 
but  this  is  no  argument  for  disregarding  the  very  interesting 
and  useful  observations  of  the  French  investigators.  The 
serologic  progression  from  the  early  stage  of  the  disease  to 
its  final  deterioration  is  as  follows: 


Serum  W.  R. 
Fluid  W.  R.. 


Incipient  Stage.    Fully  Developed.  Paretic  Decline 


Positive. 
Negative. 


Positive. 


Negative. 
Positive. 


The  globulin  content,  pleocytosis,  and  the  reducing  power 
were  not  considered  in  the  studies;  at  least  no  special  sig- 
nificance was  attached  to  them.  If  we  were  permitted  to 
formulate  a  serologic  succession  of  events  from  the  material 
analyzed  by  the  author,  the  following  arrangement  of  the 


184      SEROLOGY   OF    NERVOUS    AND   MENTAL   DISEASES 

entire    serologic  chart,   taking  into   account  the  work   of 
Marie  as  well,  would  give  the  following  result: 


Incipient  Stage. 

Fully  Developed. 

Paretic  Decline. 

Serum  W.  R 

Fluid  W.  R 

Globulin 

Positive. 

Negative. 

Excess  or  not. 

More  than  60. 
Prompt. 

Positive. 
Positive. 
Excess. 

60  or  less. 
Prompt. 

Negative. 
Positive. 
Frequently 
normal. 
Less  than  40. 
Prompt. 

Pleocytosis 

Reduction 

Although  when  these  observations  are  given  considerable 
latitude  they  are  useful,  when  viewed  critically  they  will 
furnish  sufficient  grounds  for  argument,  as  many  exceptions 
to  the  formulae  here  laid  down  will  be  found.  The  number 
of  cells  per  c.mm.  alone  will  give  rise  to  much  speculation, 
as  some  observers  will  claim  that  in  a  certain  patient  more 
than  100  and  even  200  cells  were  counted  in  the  spinal 
fluid.  All  these  exceptions  must  be  admitted,  although  the 
serologist  who  has  had  sufficient  neurologic  training  will 
perhaps  question  the  genuineness  of  a  general  paresis  that 
exhibited  over  200  cells  per  c.mm.  in  the  cerebrospinal  fluid. 
Nevertheless,  such  cases  are  seen,  just  as  scarlet  fever  with- 
out a  rash  is  occasionally  encountered,  or  as  typhoid  bacilli 
may  occur  in  the  blood-stream  without  giving  rise  to  the 
disease.  In  the  greatest  majority  of  cases,  however,  these 
findings  will  hold  good  and  prove  of  the  greatest  utility  to 
the  clinician. 

The  Gold  Chlorid  Curve 

Since  the  studies  of  Lange  concerning  the  significance  of 
the  precipitation  (Ausflockung)  of  colloidal  gold  in  the 
cerebrospinal  fluid  of  syphilitic  patients,  a  few  papers  have 
appeared  in  America,  all  attaching  great  diagnostic  signifi- 
cance to  the  appearance  of  the  reaction. 

In  the  experiments  undertaken  at  the  Neurological  Insti- 
tute it  became  apparent  that  although  no  great  amount  of 
specificity  could  be  placed  on  the  precipitation  in  all  cases 
of  neurologic  lues,  a  definite  reaction,  however,  could  be  ob- 
served in  paresis  and  in  some  cases  of  tabo-paresis.    The  tech- 


PLATE  II 


PLATE  III 


r 

CL> 

Tg. 

5 

O' 

bfi 

rt 

c3 

ft 

rs 

cc 

p 

'_?' 

~ 

£ 

'_ 

o 

'o 

o 

£ 

o 

o 

w 

'[^ 

o> 

c3 

CO 

o 

Oi 

V 

Qj 

Q 

^- 

1   CO 

aj 

s 

H"§ 


jus 


THE    GOLD    CHLORID    CURVE  185 

nic  of  the  test  was  described  in  the  first  part  of  this  volume, 
but  it  is  deemed  advisable  to  describe  here  the  meaning 
of  the  curve  and  the  color  changes,  as  well  as  the  dilutions. 

The  color  of  the  gold  solution,  as  stated  elsewhere,  is  a 
deep  red  without  the  least  trace  of  brown.  From  9  to  12 
tubes  of  various  dilutions  of  cerebrospinal  fluid,  from  1  :  10  to 
1  :  2560  or  more  are  prepared.  The  red  gold  is  placed  in 
each  tube,  and  permitted  to  remain  at  room  temperature 
over  night.  The  next  morning  some  tubes  will  show  definite 
color  changes,  which  are  designated  as  follows: 

Complete  precipitation  showing  a  water-clear,  colorless  fluid  equals .  .  5 

The  slightest  tinge  of  a  steel  gray  is  designated  as 4 

A  somewhat  deeper  shade  than  the  above  or  bluish  tinge  as 3 

A  reddish  blue  or  bluish  red  as 2 

A  red  color,  slightly  different  from  the  original  color,  as 1 

No  change  in  color  as 0 

The  numbers  are  arranged  from  5  down  to  0;  the  dilu- 
tions are  arranged  from  left  to  right,  starting  with  the  1  :  10 
tube. 

An  absolutely  negative  curve  would  present  the  following 

characters : 

5 
4 
3 
2 
1 

0 ,*    i  ,t 

oooooooooo 

\\\\i-ilO<DWlOH 

l-irJi-ir^s    V.   \  ,— I  C\>  lQ 

— ^s^^i 

The  curve  obtained  with  spinal  fluids  from  patients 
with  general  paresis  presented  the  following  general  appear- 
ance in  the  majority  of  instances: 

O  l   !   •    •   .    -   « 

oooooooooo 

-HWtoOdKM^COCDW 
'-' "  •— '  \  <  s 

From  the  previous  explanatory  remarks,  it  will  be  seen  that 
there  was  no  change  in  the  first  curve  from  the  original  color 


186      SEROLOGY   OF   NERVOUS    AND    MENTAL   DISEASES 

of  the  colloidal  gold,  which  is  a  rich  red  in  every  tube;  the 
curve  obtained  in  general  paresis,  however,  presented  an  ab- 
solutely clear  series  of  three  tubes  in  the  first  three  dilutions; 
then  a  drop  to  0,  or  no  color  change.  This  drop  and  the 
general  resemblance  to  a  step  or  series  of  steps  suggested  the 
name  "step-ladder  curve,"  by  which  term  this  particular  form 
of  precipitation  of  the  colloidal  gold  is  known  in  the  author's 
laboratory.  Although  very  suggestive  of  general  paresis, 
it  is  not  to  be  regarded  as  characteristic  without  consider- 
ing the  other  accompanying  features  of  the  serology  of  this 
disease.  Emphasis  must,  however,  be  placed  on  the  fact 
that  up  to  the  present  this  curve  has  been  very  constantly 
found  in  this  syphilitic  nervous  disorder.  The  intensity 
of  the  positive  Wassermann  and  the  other  serologic  findings, 
and,  especially,  the  clinical  corroboration  that  is  always 
to  be  had  when  the  fluid  gives  this  reaction,  make  this  curve 
one  of  the  most  important  aids  in  formulating  a  diagnosis 
of  general  paresis.  It  is  also  demonstrable  in  the  majority  of 
cases  of  tabo-paresis,  and,  like  the  other  findings,  is  not 
easily  affected  by  therapy. 

The  curve  was  also  obtained  in  a  case  of  multiple  sclerosis, 
while  in  six  others  it  was  absent.  In  cerebrospinal  lues  the 
curve  does  not  show  the  uninterrupted  series  of  colorless 
tubes  in  the  first  dilutions,  but  displays  a  rise,  then  a  fall, 
and  then  another  rise,  so  that  the  continuous  feature  is  not 
observed.  The  following  may  serve  as  an  example  of  such 
a  curve : 


OOOOOQOOOO 

'-<C\ix}<OOCOCQ<i'COCDC\l 

At  present  sufficient  results  are  not  at  hand  to  justify  the 
contention  that  a  diagnosis  of  syphilis  of  the  nervous  system 
can  be  made  after  securing  the  colloidal  gold  reaction.  In 
the  author's  experience  paresis  and  tabo-paresis  give  char- 
acteristic precipitations  with  gold  chlorid,  in  that  the  first 


PLATE  IV 


00 

>s 

'53  o 

09 

o 

S- 

ti 

-u 

0<  j3 

"3 

-£ 

■-, 

09 

o 

09 

b£ 

sL 

t4-i 

O 

09 

o 

S3 

'+= 

+a 

OB 

■- 

u 

09 

09 

+= 

> 

K 

09 

O 

XJ3 

o 

^ 

4= 

^. 

C 

ea 

c 

£ 

CO 

,fH 

s 

42 

^o 

p  a 


o  09 

09    C 

>•- 

is  (3 

05    (19 

09    & 
>    3 

O  H 


Q3     M 

^§ 

<$ 
■ft 

2  8 
°  ft 

2^  § 

o  o  g 

o  o  o) 

S^   § 
0+3    S 


.ft  "3  >> 

'3  ^    09 

£3* 


GOLD   CHLORID    REACTION    IN    GElVERAL   PARESIS      187 

one,  two,  or  more  tubes,  i.  e.,  in  the  greater  concentrations, 
show  complete  precipitation  of  colloidal  gold,  as  evidenced 
by  the  clear  color  of  the  fluid  in  these  tubes. 

A  change  in  the  curve  is  but  rarely  apparent  after  treat- 
ing a  patient  with  general  paresis,  but  as  the  observations  are 
not  extensive  enough,  the  effects  of  therapy  on  the  gold 
chlorid  curve  cannot  be  definitely  stated  at  present.  It  will 
be  of  interest  to  observe  a  number  of  "step-ladder"  curves 
as  obtained  with  the  fluids  from  patients  with  general  paresis, 
and  also  to  describe  the  other  reactions  employed  in  this 
syphilitic  neurologic  disorder.  The  curves  from  tabetics, 
tabo-paretics,  and  cerebrospinal  syphilis  patients  will  also 
be  presented  below.  The  dilutions  will  be  represented  by 
figures,  so  that  1  will  represent  a  dilution  of  -fa,  2  one  of  -%•-$ 
3  one  of  -£■$,  4  one  of  ^,  5  one  of  T|0,  6  one  of  g^¥,  7  one  of 
^|o,  etc.  The  changes  in  color  will  be  expressed  by  the 
numbers  5  to  0,  as  previously  explained.  The  serum  Was- 
sermann  reaction  will  be  abbreviated  to  S.  W.;  the  fluid 
Wassermann,  to  F.  W. ;  globulin,  to  Gl. ;  and  the  cell  content 
will  be  given  under  PL  (pleocytosis) .  In  a  number  of  cases 
the  amino-nitrogen  content  of  the  serum  will  also  be  given, 
expressed  in  milligrams  of  nitrogen  per  100  c.c.  of  serum, 
for  the  significance  of  which  the  reader  is  referred  to  the 
section  on  this  subject. 

GOLD  CHLORID  REACTION  IN  GENERAL  PARESIS 

MrCop.      1E345678910  Mr.Bec.        IS34S678910 


5      .    .  .    . 

4- 
3 
2 

1  1  \ 

0  0  \ 

SW.    F.W   Gl     PI.  Amino N.1.260       S.W      F.W        Gl  PI.     Amino  N, 

+  +  _         21  +  -J-  +  3.0  i.500 

Mr.Ha.  Mr3os. 


PI    Amino  N. 
7o     1,642 


188      SEROLOGY    OF   NERVOUS   AND    MENTAL   DISEASES 


Mr.Ro. 

5 
4 
3 

0 
S.W.  F.W 


Mr.Pr. 


Gl.  PL 

-        16 


Amino  N. 
0.320 


sw 


Mr.Sla.       123456789  iO 


5 

1 
0 

F.W 

+ 


sw 


GL 


PI. 

24 


Mr.Bro. 


aw 


Gl 

PI.    Amino N. 
0        1A86 

1 

2  3  4   5  6  7   8 

5      . 

4     "" 

3 

Z 

1 

0 

V    8    '. 

FW 

4 

Gl.    PI 

+        53 

8  9  10 


Mr.Kar. 


Mr.Bra. 


SW  F.W     Gl 
+         + 


SW      F.W 


MrHur. 


MrMcM. 


5     . 

•     •    .! 

5      . 

•    .    . 

4    " 

4- 

\ 

3 

\ 

3 

\ 

2 

\ 

Z 

\ 

1 

\ 

1 

\ 

0 

Gl. 

&w. 

0 
F/W 

Gl. 

v ..... . . 

SW.  F.W. 

PI. 

PI. 

+          4 

+ 

8 

— 

— 

— 

23 

The  contrast  between  the  genuine  general  paresis  gold 
precipitation  and  the  reactions  obtained  in  the  other  syph- 
ilitic diseases  of  the  nervous  system,  at  least  as  observed  in 
the  laboratory  of  the  Neurological  Institute,  will  reveal  at  a 
glance  the  importance  of  these  tests.  There  are,  of  course, 
exceptions,  in  that  some  paretics  do  not  react  in  the  char- 
acteristic manner,  but  these  cases  are  few,  comprising  less 
than  10  per  cent,  of  those  analyzed.  Only  one  case  of 
cerebrospinal  lues  and  one  of  multiple  sclerosis  gave  this 
curve.    In  the  former  over  500  lymphocytes  per  c.mm.  were 


GOLD    CHLORID    REACTION    IN   GENERAL  PARESIS      189 

obtained,  which,  in  the  author's  opinion,  is  quite  sufficient 
to  exclude  general  paresis,  and,  so  far  as  multiple  sclerosis 
is  concerned,  the  author  believes  that  one  is  rarely  called 
upon  to  decide  between  this  disease  and  general  paresis, 
so  that  the  curve  obtained  will  not,  and  in  the  given  instance 
did  not,  influence  the  diagnosis  of  multiple  sclerosis  in  the 
least. 

The  precipitation  in  tabes  shows,  in  the  majority  of  in- 
stances, the  following  curves: 

MrWei  123^587  89  10  M*St  1  2  3  *   5  6  7   8  9  10 

5  5 


0        a,  0 


The  advent  of  paresis  or  tabo-paresis  is  represented  by  a 
curve  that  is  very  suggestive  of  the  general  paresis  curve, 
being  another  corroborative  biologic  phenomenon  in  favor 
of  the  earlier  appearance  of  laboratory  signs  in  the  very  be- 
ginning of  paresis  rather  than  the  development  of  clinical 
symptoms. 

Mi-Man.  Mr.Car 

0  \ 0 

In  cerebrospinal  lues  the  curve  is  also  quite  different  from 
the  general  paresis  "step-ladder"  appearance. 

Mr.Hut  MT.Hanr. 

5  5 

4-  4 

3       j.  3 

0  \_.  0         ^^^L_i_1_j_i_x_t_» 


The  opinion  of  Lange  and  of  those  who  followed  him  in 
experimenting  with  fluids  from  patients  with  syphilitic 
affections  of  the  nervous  system,  that  there  is  a  specific  pre- 


190      SEROLOGY   OF   NERVOUS   AND    MENTAL   DISEASES 

cipitation  of  the  colloidal  gold  in  cerebrospinal  fluids  from 
such  patients,  must,  as  the  result  of  Dr.  McClelland's  and 
of  the  author's  experience,  be  modified  considerably  before 
it  can  be  accepted  in  toto.  The  curve  does  not  depend  upon 
the  protein  content  of  the  cerebrospinal  fluid,  as  some  fluids 
without  an  excess  showed  the  curve  and  some  with  a  very 
marked  excess  gave  no  curve  whatever.  A  similar  result  was 
obtained  with  tabetics  who  gave  no  reaction  of  an  excess, 
and  also  with  patients  with  cord  tumors,  who  showed  the 
presence  of  a  marked  protein  excess.  The  raison  d'etre  of 
the  reaction  must  remain  in  abeyance  for  the  present,  as 
no  satisfactory  explanation  has  been  offered  to  cover  all  the 
peculiarities  of  the  test. 

The  Serologic  Differentiation  Between  Lues  Cerebro- 
spinalis  and  general  paresis 

As  the  result  of  a  wide  experience  with  neurologic  mate- 
rial, coupled  with  the  services  of  a  serologic  laboratory, 
Nonne  made  the  attempt  to  differentiate,  serologically, 
between  the  two  diseases — cerebrospinal  lues  and  general 
paresis — that  at  times  present  difficulties  to  the  clinician. 
His  serologic  analysis  of  the  two  diseases  is  as  follows: 

Paresis  or  Taboparesis.  Cerebrospinal  Syphilis. 

Serum   Wassermann   positive    (in  Serum    Wassermann  positive   (in 

almost  100  per  cent.).    Spinal  nearly  80  to  90  per    cent.). 

pressure  frequently  increased.  Spinal     pressure     often     in- 
creased. 

Phase  1  positive  (in  nearly  95  to  Phase    1    only   exceptionally   ab- 

100  per  cent.).  sent. 

Lymphocytosis  (in  nearly  95  per  Lymphocytosis,  like  phase  1,  usu- 

cent.).  ally  present. 

Wassermann  reaction  in  fluid  posi-  Wassermann  reaction  positive  in 

tive  in  about  85  to  90  per  about  10  per  cent,  of  fluids, 

cent.,  using  0.2  c.c.  using  0.2  c.c. 

Using  larger  amounts — plus  in  100  Using  larger  amounts — nearly  al- 

per  cent.  ways  plus. 

This  attempted  differentiation  between  general  paresis 
and  cerebrospinal  syphilis,  as  offered  by  the  eminent  German 
worker,  falls  short  of  its  purpose.  Upon  close  analysis  of 
Nonne's  table,  one  is  at  a  loss  to  determine  upon  what  special 
feature  in  either  disease  he  places  the  greatest  reliance. 
In  both  conditions  the  blood-serum  is  very  rarely  negative 


JUVENILE   PARESIS  191 

to  the  Wassermann  test.  The  same  is  true  of  the  spinal  fluid. 
The  phase  1  is  present  in  one  to  the  extent  of  100  per  cent., 
and  in  the  other  it  is  only  exceptionally  absent.  The  same 
is  true  of  the  lymphocytosis.  The  only  possible  differentiat- 
ing feature  is  obtained  when  but  0.2  c.c.  of  spinal  fluid  is 
used  in  testing  for  the  Wassermann  reaction,  for  then  it 
will  be  obtained  in  almost  90  per  cent,  of  cases  of  general 
paresis,  and  in  only  10  per  cent,  of  those  of  cerebrospinal 
syphilis,  a  feature  that  is  obliterated  when  using  larger 
quantities. 

If  the  clinician  should  be  compelled  to  seek  the  laboratory's 
aid  in  clearing  up  a  difficult  case  of  neurologic  syphilis,  and 
particularly  if  he  sought  to  differentiate  between  general 
paresis  and  cerebrospinal  syphilis,  the  author  is  convinced 
that  very  little  help,  if  any,  would  be  obtained  from  the 
table  just  given.  The  points  of  difference,  as  they  appear 
from  an  analysis  of  the  material  collected  in  this  exposition 
of  the  subject,  would  be  as  follows,  not  including  cases  that 
were  treated  with  specific  remedies : 

UNTREATED  CASES  OF 
General  Paresis.  Cerebrospinal  Syphilis. 

Serum  Wassermann  plus  in  90.9     Plus  in  88.7  per  cent. 

per  cent. 
Fluid   Wassermann   plus   in   75.3     Plus  in  32.7  per  cent. 

per  cent.,  using  from  0.2  to 

0.5  c.c. 
Globulin  excess  in  86.7  per  cent.       Excess  in  50.3  per  cent. 
Pleocytosis,  as  a  rule,  less  than  100     Pleocytosis  usually  more  than  100 

cells  per  c.mm.,  and  obtained  per    c.mm.,    and    present    in 

in  96.2  per  cent,  of  cases.  96.7  per  cent,  of  cases. 

Fehling  reduction  prompt  in  100     Sometimes  absent. 

per  cent. 
"Step-ladder"     gold     curve     ob-     Present  in  less  than  5  per  cent,  of 

tained  in  over  90  per  cent,  of  cases. 

cases. 

Juvenile  Paresis 

The  occurrence  of  juvenile  paresis,  which  must  be  con- 
sidered as  a  disease  produced  by  syphilis  in  the  parents, 
disposes,  in  the  great  majority  of  instances,  of  the  possi- 
bility conceived  by  some  workers  that,  for  the  production 
of  this  disease,  a  special  variety  of  the  Treponema  pallidum 
is  necessary.  In  the  cases  observed  and  reported  upon  by 
Plaut  no  luetic  parental  data  could  be  obtained.     That 


192      SEROLOGY    OF   NERVOUS    AND   MENTAL   DISEASES 

such  parents  may  have  had  syphilis  in  some  form  that  was 
kept  from  observation  as  the  result  of  proper  treatment  is 
possible,  but  this  is  not  the  case  with  paresis,  which  is  sooner 
or  later  diagnosed  with  accuracy  and  easily  elicited  from 
the  anamnesis.  In  other  words,  juvenile  paresis  is  not  neces- 
sarily dependent  upon  the  existence  of  paresis  in  the  parents, 
but  may  be  the  result  of  any  variety  of  syphilis,  whether 
vascular,  visceral,  or  osseous. 

The  following  case  is  that  of  a  youth  of  twenty,  an  errand 
boy,  born  in  the  United  States.  He  was  brought  to  the 
Institute  on  account  of  trouble  with  his  eyes : 

Previous  History. — One  of  five  children,  who  are  all 
healthy.  A  brother  next  older  to  the  patient  is  a  periodic 
drinker.  Patient  went  to  school  at  five,  but  did  not  progress 
well.  When  about  six  he  began  to  play  truant.  In  his 
ninth  year  the  patient  complained  of  an  inability  to  see 
print  or  to  write.  Began  to  smoke  cigars  at  ten,  and  left 
school  at  thirteen.  Associated  with  men  of  questionable 
character.  His  father  having  been  in  the  liquor  business, 
the  boy  began  to  use  alcoholics  to  an  inordinate  degree.  His 
eye-sight  kept  getting  worse.  When  examined  physically 
he  showed  no  pupillary  response  to  light;  right  pupil  very 
irregular.  Corneal  sensibility  reduced  in  both  eyes;  mobility 
normal;  no  nystagmus;  no  diplopia.  Vision  R.,  no  percep- 
tion; L.,  2§o-  Fundi,  simple  optic  nerve  atrophy,  more 
marked  in  right.  Mentality  that  of  a  boy  of  nine  (Binet 
test).  Cannot  repeat  test  sentences  correctly.  Station  nor- 
mal; some  tremor  of  upper  extremities;  apparent  ataxia  of 
lower  extremities.  When  told  to  perform  certain  acts, 
often  did  the  opposite.  Complete  pharyngeal  anesthesia. 
No  tremor  of  tongue.  Abdominal  and  epigastric  reflexes 
present  and  equal.  Knee-jerks  elicited  with  difficulty. 
Flexor  plantar  response.  The  changes  in  the  reflexes  are 
not  accompanied  by  any  palsies,  such  as  might  be  present  in 
a  multiple  neuritis.  Teeth  show  Hutchinsonian  charac- 
teristics.   Facial  asymmetry. 

This  case,  although  presenting  distinct  irregularities, 
was,  upon  the  strength  of  the  serologic  report,  diagnosed  as 
one  of  juvenile  paresis.    He  gave  a  positive  serum  and  fluid 


THERAPY  ON  THE  SEROLOGY  OF  GENERAL  PARESIS   193 

Wassermann,  an  excess  of  globulin,  and  8  cells  per  c.mm., 
together  with  a  typical  gold  chlorid  curve.  (See  Mr.  Hur 
under  Gold  Chlorid  Test.)  The  assurance  the  physician 
receives  from  such  an  analysis  is  self-evident,  and  removes 
all  doubt  from  his  mind  as  to  the  underlying  cause  of  the 
disease.  This  patient  emphatically  denied  all  knowledge  of 
an  infection.  The  patient's  mother  shows  diminished  in- 
telligence, has  pupils  that  do  not  react  to  light,  and  gave  a 
positive  Wassermann  reaction  in  the  serum. 

The  Influence  of  Therapy  on  the  Serology  of 
General  Paresis 

This  subject  is  discussed  not  so  much  with  the  purpose 
of  showing  what  improvement  can  be  accomplished  clinically 
in  this  disease, — a  subject  that  will  be  presented  in  a  subse- 
quent part  of  this  volume, — but,  rather,  for  the  purpose  of 
showing  to  what  extent  one  can  change  the  serology  or 
render  a  positive  Wassermann  negative  by  instituting 
strenuous  therapeutic  measures.  A  careful  study  of  the 
''Wassermann  fast"  quality  of  general  paresis  will  shed  a 
great  deal  of  light  upon  the  conception  of  the  serologic 
progression  of  a  syphilitic  disorder  from  cerebrospinal 
lues  or  tabes  to  general  paresis.  Bearing  in  mind  the  Dar- 
winian dictum  that  "  Natura  non  facit  saltum,"  it  is  incum- 
bent upon  the  physician  to  regard  as  important  the  "Was- 
sermann fast"  quality  of  his  patient's  serum.  Even  though 
the  patient  may  at  this  time  show  no  clinical  manifestations 
of  the  disease,  such  as  speech,  memory,  or  character  defects, 
the  serum,  nevertheless,  takes  on  a  peculiarity  that  is  present 
most  strikingly  in  general  paresis.  This  similarity  is  in 
itself  sufficient  to  warrant  placing  the  patient  under  rigid 
observation  and  treatment;  in  other  words,  it  is  the  phys- 
ician's duty  to  overcome  as  quickly  as  possible  the  "Was- 
sermann fast"  tendency  of  the  patient's  serum.  It  is  the 
author's  conviction  that  the  treatment  that  is  capable  of 
overcoming  a  positive  Wassermann  reaction  in  the  fluid  and 
serum  is  much  more  valuable  and  of  greater  significance  to 
the  patient  than  is  the  complete  removal  of  the  pleocytosis. 
The  latter  is  only  a  sign  of  meningeal  irritation,  whereas  the 

13 


194      SEROLOGY    OF    NERVOUS   AND    MENTAL    DISEASES 

former  is  "the  writing  on  the  wall"  that  will  sooner  or  later 
claim  its  victim.  Timely  and  vigorous  interference  may 
in  some  instances  avert,  or  at  least  postpone,  the  danger. 

Patient    O.    presented    before    treatment    the    following 
serology : 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Positive. 

Positive. 

Positive. 

11  cells. 

Prompt. 

Upon  receiving  this  report  treatment  was  instituted,  and 
0.6  gm.  salvarsan  was  administered  intravenously.  The 
serology  obtained  five  weeks  later  showed: 


Sekum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Positive. 

Positive. 

Positive. 

11  cells. 

Prompt. 

A  similar  dose  of  salvarsan  was  administered  one  week 
after  the  last  serologic  examination,  and  another  serologic 
analysis  made  after  two  weeks.    This  showed: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Positive. 

Positive. 

Positive. 

10  cells. 

Prompt. 

A  third  intravenous  injection,  given  immediately  after 
the  performance  of  the  tests,  followed  by  a  serologic  study 
one  week  after  the  treatment,  gave: 


Serum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocttosis. 

Reduction. 

Weakly 
positive. 

Positive. 

Positive. 

7  cells. 

Prompt. 

Despite  the  normal  cell  count  obtained  in  the  fluid,  the 
treatment  cannot  be  considered  successful,  as  enough 
factors  still  exist  in  the  patient's  body  to  supply  sufficient 


RESUME   AND   REMARKS  195 

"reagins"  for  the  persistence  of  the  positive  Wassermann 
in  the  fluid  and  to  a  lesser  extent  in  the  serum. 

With  the  ordinary  methods  of  introducing  salvarsan  into 
the  system,  and  with  the  present  dosage,  number  of  injec- 
tions, and  duration  of  treatment-free  intervals,  the  disease 
process  still  continues  its  progress  unabated,  as  is  shown  by 
the  persistent  Wassermann.  The  foregoing  serologic  study 
is  only  one  of  many  in  which  approximately  the  same  result 
as  the  one  cited  was  obtained.  Concerning  the  different 
methods  of  treating  this  malady,  the  reader  is  referred 
to  the  section  on  Treatment. 

Resume  and  Remarks 

An  analysis  of  the  serology  of  general  paresis  conveys  the 
impression  that  of  all  syphilitic  diseases  of  the  central  ner- 
vous system,  this  disease,  when  it  does  present  a  positive 
Wassermann  in  the  serum  in  particular,  and  in  the  spinal 
fluid,  to  a  lesser  extent,  will  give  the  reaction  in  its  greatest 
intensity.  It  also  possesses  the  quality  that  has  been  termed 
"Wassermann  fast,"  in  that  it  is  very  difficult  to  secure  a 
negative  result  by  means  of  treatment.  This  peculiarity  is 
occasionally  present  also  in  the  other  syphilitic  diseases  of 
the  nervous  system,  and  when  it  occurs,  is  to  be  considered 
as  a  "Signum  mali  ominis"  The  transition  from  cerebro- 
spinal lues  to  general  paresis  is  preceded  by  the  "Wassermann 
fast"  reaction,  and  the  same  is  true  also  of  the  transition  or 
the  advent  of  a  tabo-paresis.  The  decrease  in  the  number 
of  cells  in  a  case  of  cerebrospinal  syphilis,  without  influenc- 
ing the  positive  serum  Wassermann,  bears  out  the  concep- 
tion of  Marie  of  the  serology  of  general  paresis  in  its  early 
stage,  particularly  when  ushered  in  with  a  cerebrospinal 
lues  of  the  "Plaut  type." 

In  the  light  of  modern  research  serologic  methods  permit 
us  to  differentiate  between  cerebrospinal  lues  and  general 
paresis,  provided  the  typical  serology  is  obtained  where  the 
clinical  opinion  is  uncertain.  Where  the  serology  is  dubious, 
as  it  not  infrequently  is,  a  waiting  policy  is  best,  or  therapy 
may  be  instituted  regardless  of  the  uncertainty  that  exists  as 
to  the  final  diagnosis.    Treatment  may,  in  fact,  help  consider- 


196      SEROLOGY   OF   NERVOUS    AND   MENTAL   DISEASES 

ably  in  deciding  for  one  or  the  other  disease,  as  was  sug- 
gested on  a  previous  page.  It  is  not  at  all  difficult  to  ascer- 
tain the  cause  for  a  persistent  Wassermann  reaction  in  a 
paretic  patient.  If  we  regard  the  luetic  process  from  the 
locality  affected,  we  will  see  that  in  general  paresis  the 
amount  of  protection  given  to  the  Treponema  pallidum  is 
much  greater  than  in  the  other  syphilitic  diseases  of  the  ner- 
vous system.  If  the  process  is  situated  in  the  cerebral 
cortex  proper  drugs  injected  into  the  veins  will  have  little 
chance  of  reaching  the  walled-in,  inaccessible  microorgan- 
isms; hence  the  formation  of  necessary  reagins  for  the 
existence  of  a  positive  Wassermann  is  ideal  and  almost 
constant. 

The  process  that  permits  the  appearance  of  a  "Wasser- 
mann fast"  state  may  be  regarded  as  a  migration  of  the 
treponema  from  accessible  to  deeper,  inaccessible  brain 
portions,  establishing  a  depot  for  reagins,  and  forming  the 
histologic  nucleus  for  a  future  general  paresis.  How  long 
a  time  a  "Wassermann  fast"  state  must  exist  before  clinical 
features  of  the  disease  manifest  themselves,  or,  expressing 
the  hypothesis  in  its  histologic  equivalent,  how  much  of 
the  brain  substance  must  be  involved  before  paretic  symp- 
toms present  themselves,  is  a  problem  worthy  of  investiga- 
tion. 

It  may  safely  be  predicted  that  the  gold  chlorid  curve 
("step-ladder  curve")  will  occupy  a  prominent  place  in  the 
detection  of  the  foregoing  tendency,  as  evidenced  by  the 
presence  of  this  reaction  in  tabo-paresis.  It  is  not  char- 
acteristic of  syphilis  of  the  nervous  system  in  general,  but 
is  very  constantly  present  in  general  paresis.  Tabes  does 
not  give  it  and  neither  does  cerebrospinal  lues. 

In  the  study  of  psychiatric  material  one  is  frequently  called 
upon  to  differentiate  between  post-traumatic  psychosis  and 
general  paresis.  In  these  cases  one  must  consider  the  pos- 
sible coexistence  of  a  visceral  lues,  a  fact  which  should  not 
confuse  the  investigator.  If  the  fluid  is  negative,  the  chances 
are  against  the  diagnosis  of  general  paresis,  although  nega- 
tive fluids  are  not  impossible  in  general  paresis.  If  doubt 
exists,  the  gold  chlorid  is  made  use  of,  which  would,  in  the 


SEROLOGY    OF   EARLY    LUES    AND    ITS    SIGNIFICANCE      197 

majority  of  instances,  decide  the  diagnosis;  if,  however,  this 
proves  unsatisfactory,  then  the  resistence  to  therapy  of  the 
positive  serum  Wassermann  should  be  taken  into  account. 
With  our  present  development  of  serologic  methods,  it  is 
hardly  possible  to  err  in  the  exclusion  of  a  non-luetic  disease 
of  the  nervous  system. 

In  the  alcoholic  psychosis  (pseudoparesis)  one  finds  no 
difficulty  in  differentiating  the  condition  from  general  paresis, 
and  the  same  is  true  of  the  manic-depressive  psychosis. 
Some  paranoid  forms  of  general  paresis  may  give  rise  to 
confusion,  although  the  interpretation  is  not  difficult. 

The  Serology  of  Early  Lues  and  its  Significance 

Frequent  mention  was  made,  on  previous  pages,  of  the 
early  involvement  of  the  nervous  system  by  the  syphilitic 
process.  It  is  not  at  all  a  rash  statement  to  make  that  in 
many  cases  the  Treponema  pallidum  is  present  in  the 
vicinity  of  the  brain  and  cord  at  as  early  a  date  as  is  the 
ulcus  durum.  This  fact  has  been  brought  out  by  many 
clinical  observers,  among  the  earliest  being  Ravaut.  Plaut 
mentions  the  fact  that  he  observed  a  syphilitic  cerebral 
meningitis  in  a  patient  whose  initial  lesion  had  not  yet 
healed.  The  autopsy  showed  a  nodular  syphilitic  meningitis 
limited  to  the  base.  The  serum  of  this  patient  gave  a  nega- 
tive Wassermann  reaction. 

In  the  future  the  syphilographer  will  be  able,  with  the  aid 
of  serologic  methods,  to  classify  his  syphilitic  patients  into 
groups,  such  as  those  who  will  possibly  develop  syphilis 
of  the  nervous  system,  and  those  who  are  not  likely  to. 
Cases  in  which  the  changes  in  the  serum  and  fluid  justified 
a  diagnosis  of  cerebrospinal  lues  in  a  patient  not  entirely 
free  from  syphilitic  rash  are  not  rare.  The  number  of 
patients  with  an  initial  lesion  still  active  who  would  show  a 
cell  count  and  a  positive  fluid  Wassermann  has  never  been 
determined.  It  is  plausible  to  believe  that  the  Treponema 
pallidum  permeates  the  entire  system  of  a  patient  in  the 
beginning  of  the  disease,  gradually  settling  in  various  tis- 
sues, which  will  later  determine  the  type  of  luetic  affection, 
as,  e.  g.,  visceral,  vascular,  cutaneous,  nervous,  etc.     The 


198      SEROLOGY  OF   NERVOUS  AND   MENTAL   DISEASES 

factors  that  determine  the  permanent  involvement  of  the 
nervous  system  are  still  unknown.  It  is,  however,  a  safe 
procedure  to  treat  the  patient  with  a  positive  spinal  fluid 
more  energetically,  and  continue  the  therapy  until  all 
pathologic  constituents  have  disappeared  from  the  cerebro- 
spinal fluid.  This  applies  particularly  to  the  "chancres 
cephaliques"  of  the  French,  who  give  a  large  percentage 
of  cases  of  involvement  of  the  nervous  system.  The  possi- 
bility of  diminishing  the  number  of  cases  of  tabes,  cerebro- 
spinal lues,  or  general  paresis  is  in  the  hands  of  the  physician 
who  sees  the  initial  lesion  and  bears  in  mind  the  early  possi- 
bility of  involvement  of  the  central  nervous  system,  and  the 
concomitant  evidence  to  be  found  in  the  cerebrospinal 
fluid  in  such  cases. 

If  the  prophylactic  treatment  of  syphilitic  diseases  of  the 
nervous  system  is  ever  to  become  a  certainty,  it  will  have  to 
be  introduced  by  the  syphilidologist  or  the  genito-urinary 
specialist,  who,  as  a  rule,  see  such  cases  first.  With  this  aim 
in  view,  it  will  be  just  as  necessary  for  these  physicians  to 
acquaint  themselves  with  the  various  serologic  manifesta- 
tions of  lues,  particularly  of  early  lues  of  the  nervous  system, 
as  it  is  obligatory  for  the  neurologist  to  know  the  changes 
that  occur  in  the  cerebrospinal  fluid.  In  .an  instructive  study 
of  the  changes  that  take  place  in  the  cerebrospinal  fluid  in 
the  various  stages  of  syphilis,  Wilhelm  Gennerich  has  arrived 
at  the  very  important  conclusion  that  in  many  cases  of 
primary  lues  the  cerebrospinal  fluid  shows  evidences  of  in- 
fection, which,  according  to  his  opinion,  is  an  expression  of 
the  peculiarity  of  the  syphilitic  virus,  in  that  it  shows,  by 
involving  the  nervous  apparatus,  its  tendency  to  spread  and 
permeate  the  human  body.  This  tendency  to  extension  is 
inherent  in  the  Treponema  pallidum,  whether  held  in  check 
by  immune  processes  or  by  appropriate  therapy.  Hence  the 
active  manifestations  that  occur  in  a  luetic  after  a  compara- 
tively symptom-free  period.  The  temporary  inertness  of 
the  virus  is  to  be  noted  in  ophthalmologic  practice,  where, 
suddenly,  an  eye  muscle  becomes  affected;  here,  apparently, 
the  natural  immune  protection  which  sufficed  to  keep  the 
treponema  dormant  and  confined  for  a  prolonged  period  was 


SEROLOGY   OF   EARLY    LUES   AND   ITS   SIGNIFICANCE      199 

suddenly  relaxed,  with  a  resulting  activity  of  the  micro- 
organisms. Such  occurrences  are  frequently  the  mode 
of  infection  in  congenital  lues.  It  is  sufficient  to  know  that 
the  syphilitic  virus  can  lodge  in  the  meninges  very  early, 
remain  dormant  for  a  time,  and  later  manifest  its  presence 
by  a  cranial  nerve  palsy,  an  Argyll-Robertson  pupil,  absent 
knee-jerks,  defective  memory,  or  a  speech  disturbance. 
These  abnormalities,  if  detected  in  their  incipiency,  are  not 
infrequently  amenable  to  abortive  treatment.  One  of  the 
most  reliable  signs  of  an  involvement  of  the  central  nervous 
system  is  the  pathologic  status  of  the  cerebrospinal  fluid. 

In  presenting  a  case  of  cerebral  syphilis  that  occurred  six 
months  after  the  initial  lesion,  Gregory  and  Karpas  quote 
Lannois,  Fournier,  Mingazzini,  Oppenheim,  Nonne,  and 
Gowers,  all  of  whom  reported  cases  of  cerebral  lues  occurring 
from  six  weeks  to  eighteen  months  after  the  chancre. 

Nonne  speaks  of  a  case  of  basal  meningitis  that  occurred 
four  months  after  the  infection  in  a  patient  who  still  pre- 
sented a  papular  eruption.  It  must  be  remembered  that  the 
papular  form  of  syphilids  is  more  apt  than  any  other  early 
luetic  lesion  to  show  future  involvement  of  the  nervous 
system. 

The  case  reported  by  Gregory  and  Karpas  contracted  lues 
in  the  early  part  of  May,  1912.  On  June  29th  papules 
appeared  over  the  entire  body,  and  the  mucous  membrane  of 
the  throat  was  congested.  The  patient  was  first  seen  by  the 
neurologists  on  October  6th  of  the  same  year.  It  is  highly 
probable  that  the  cerebral  manifestations  were  present  in  a 
latent  form  before  the  patient  presented  a  dull  and  drowsy 
appearance  and  a  partially  paralyzed  right  side.  The 
papular  eruption  was  present,  although  it  had  disappeared 
for  a  time  as  a  result  of  antisyphilitic  therapy.  The  pupils 
were  unequal  and  slightly  irregular.  Reaction  to  light  and 
accommodation  were  sluggish.  The  right  side  of  the  face 
was  paralyzed,  and  the  nasolabial  fold  was  obliterated.  On 
the  right  side  a  clonus  and  a  Babinski  reflex  were  elicited. 
The  patient  was  bedridden  and  required  constant  attention. 
He  vomited  and  complained  of  headache.  His  serologic 
analysis  gave  the  following  results: 


200      SEROLOGY    OF    NERVOUS   AND    MENTAL   DISEASES 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Positive. 

Excess. 

618    lymphocytes 
per  c.mm. 

The  serology  here  is  unquestionably  that  of  cerebral  lues 
of  an  active  exudative  type. 

This  case  is  interesting  not  only  because  it  serves  as  an 
example  of  early  involvement  of  the  nervous  system,  but 
also  from  the  therapeutic  possibilities  that  exist  in  such 
cases.  This  patient  received,  from  October  19th  to  Decem- 
ber 18th,  7851  grains  of  potassium  iodid,  10j  grains  of  mer- 
cury salicylate,  and  1.2  gm.  each  of  salvarsan  and  of  neo- 
salvarsan.    The  subsequent  serology  showed: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Weakly 
positive. 

Positive. 

Normal. 

17  per  c.mm. 

Dreyfus'  studies  show  that  of  22  cases  of  secondary  syph- 
ilis, 17  exhibited  pathologic  changes  in  the  cerebrospinal 
fluid.  It  is  important  to  note  the  fact  that  in  these  cases 
Dreyfus  could  find  no  symptoms  suggestive  of  an  involve- 
ment of  the  central  nervous  system.  He  cites  the  case  of 
a  female  who  contracted  lues  in  January,  1912,  and  a  month 
later  presented  a  maculopapular  eruption.  There  were  no 
signs  of  involvement  of  the  nervous  apparatus,  but  the  sero- 
logic analysis  showed  that  the  fluid  was  abnormal,  as  may 
be  seen  from  the  following  table: 


Sebum  W.  R. 

Fluid  W.  R. 

Globulin. 

Pleocytosis. 

Positive. 

Negative. 

Slight. 

458  cells  per  c.mm. 

The  importance  of  making  early  serologic  tests  by  those 
who  see  syphilis  in  its  first  stages  is  self-evident.  In  these 
patients  it  cannot  be  doubted  that  proper  tests  will  greatly 
diminish  the  statistics  of  the  future  of  cases  of  tabes  and 
general  paresis,  as  well  as  of  cerebrospinal  lues. 


PART   IV 

THE  THERAPEUTIC  USE  OF  SALVARSAN 
HISTORY  AND  DEVELOPMENT  OF  SALVARSAN 

The  history  of  the  development  of  salvarsan  and  its  ap- 
plication to  the  treatment  of  syphilis  must  be  considered 
together  with  the  development  of  organic  arsenical  prepara- 
tions. Of  these,  atoxyl  deserves  first  mention.  Chemically 
speaking,  this  substance  is  para-amido-phenyl-sodium  arsen- 
ate, and  structurally  it  shows  the  following  constitution: 

/OH 
As=0 
I   \)Na 

/C\ 
HC         CH 

I  I 

HC         CH 

\/ 

I 
NH2 

Atoxyl  was  used  extensively  in  the  treatment  of  infec- 
tions due  to  the  trypanosomes.  Schaudinn,  the  discoverer 
of  the  microorganism  of  syphilis,  advanced  the  hypothesis 
that  the  organism  known  as  the  Spirochseta  pallida  stands  in 
close  relationship  to  the  trypanosomes.  Working  on  this 
hypothesis,  Uhlenhuth  experimented  with  atoxyl  in  fowl 
spirillosis,  and  obtained  sufficient  success  to  warrant  its 
trial  in  experimental  syphilis.  Here  must  be  mentioned 
also  the  contemporaneous  efforts  of  Neisser  and  of  Metchni- 
koff,  who  proved  the  great  value  of  atoxyl  in  the  treatment, 
and  even  in  the  prophylaxis,  of  animal  syphilis.  These 
results  were  chiefly  responsible  for  the  employment  of  atoxyl 
in  the  treatment  of  human  syphilis.  The  beneficial  results 
obtained  in  some  instances  of  lues,  particularly  in  those 

'?01 


202      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

forms  of  the  disease  designated  as  malignant,  served  as  a 
stimulus  to  the  clinician  and  experimenter. 

The  clinician  soon  discovered  the  fact  that  atoxyl,  while 
possessing  marked  curative  qualities,  also  produced  in  some 
instances  by-effects  serious  enough  to  preclude  its  use  in 
certain  forms  of  lues.  The  gastro-intestinal  irritation, 
nephritis,  and  occasional  blindness  that  followed  the  use  of 
this  remedy  greatly  minimized  its  therapeutic  utility. 
Even  very  minute  doses  were  frequently  followed  by  symp- 
toms of  a  toxic  nature,  so  that  Buschke  expressed  the  opinion 
that,  owing  to  its  great  toxicity,  the  usefulness  of  atoxyl  is 
almost  nil,  a  view  with  which  many  foremost  clinicians  were 
in  accord.  In  spite  of  these  failures,  Uhlenhuth  and  Manteu- 
fel  still  maintain  that  atoxyl  is  a  valuable  remedy  in  human 
syphilis.  These  investigators  have  suggested  combining 
atoxyl  with  mercury. 

Ehrlich  established  the  very  important  fact  that  during 
the  course  of  his  studies  with  the  trypanosomes  the  com- 
bined use  of  mercury  and  the  arsenical  preparation  increased 
the  sterilizing  potency  of  the  latter  to  a  marked  degree. 
The  reports  on  the  animals  treated  with  this  combination 
showed  that  very  large  doses  were  necessary  to  secure  a  cura- 
tive effect,  and  that  the  method  could  not,  therefore,  be 
utilized  in  the  treatment  of  human  syphilis.  As  a  result, 
the  use  of  atoxyl  was  discontinued. 

Another  drug  was  next  tried  for  a  short  time,  and  better 
results  expected  on  account  of  its  greater  stability;  this  was 
arsacetin.  Although  less  toxic  than  atoxyl,  this  chemical 
substance  did  not  fulfil  the  requirements  of  an  ideal  remedy 
for  lues,  and  was  likewise  discarded.  We  are  now  approach- 
ing the  chemical  relatives  of  salvarsan,  and  the  first  of  this 
group   is   arseno-phenyl-glycin.     Its   chemical    constitution 

is  as  follows: 

CH.CNHJCO  CH,(NH,,CO 

HC         CH  HC         CH 


A 


HC         CH  HC         CH 

\c/  \c/ 

I  I 

As-  ^=As 


HISTORY  AND   DEVELOPMENT   OF   SALVARSAN         203 

This  substance  is  of  interest  from  the  chemical  point  of 
view,  in  that  it  illustrates  the  trivalent  state  of  the  arsenic 
molecule.  It  should  be  remembered  that  the  arsenic  in  a 
pentavalent  state  is  less  active  in  exerting  its  toxic  in- 
fluence on  the  spirillum  group  than  when  it  is  in  a  trivalent 
state.  This  is  due  partly  to  the  fact  that  in  a  molecule  in 
which  all  the  valences  are  satisfied  the  desired  influence  is 
less  likely  to  take  place  than  when  some  of  the  valences  are 
not  satisfied,  a  fact  that  is  somewhat  analogous  to  the  readi- 
ness with  which  oxygenation  can  be  obtained  with  an  oxygen 
molecule  as  it  exists  in  H202,  where  the  O  molecules  inter- 
change valences  and  hence  are  in  a  less  stable  chemical  state 
than  when  the  O  is  attached  to  two  separate  univalent  mole- 
cules, or  one  bivalent  molecule,  as  is  the  case  in  H20  or  in 
CaO.  It  is  well  known  that  in  the  two  last-named  substances 
the  oxygen  is  separated  with  much  greater  difficulty  than  in 
the  case  of  hydrogen  dioxid.  The  same  holds  true  to  a 
certain  extent  of  arsenic  in  a  trivalent  condition;  this  inter- 
changes valences  with  its  fellow  on  the  other  side,  thus 
minimizing  the  affinity  to  the  benzol  ring,  from  which  it 
separates  when  the  suitable  opportunity  is  at  hand.  Arseno- 
phenylglycin  was  used  with  some  success  in  combating 
recurrent  fever. 

Arsenophenol  is  another  chemical  compound  that  was  tried 
with  a  view  to  obtaining  a  satisfactory  spirillocidal  sub- 
stance. Its  formula  is  the  simplest  of  any  of  the  organic 
arsenicals,  and  shows  the  following  structure: 


As 

As 

1 

/C\ 

HC    CH 

HC    CH 

HC    CH 

HC    CH 

\C/ 

\c/ 

OH 

1 
OH 

In  this  the  arsenic  is  also  in  a  trivalent  state,  and  is  very 
active  against  the  fowl  spirilloses.  It  is,  however,  very 
readily  oxydizable,  and  must  be  kept  in  vacuum  tubes. 
In  spite  of  this  precaution,  it  is  necessary  to  reduce  the  sub- 


204      SEROLOGY   OF    NERVOUS    AND    MENTAL   DISEASES 

stance  before  it  is  actually  used,  and  for  this  purpose  hydro- 
gen sulphite  (H2SO3)  is  recommended. 

Tetrachlor-  and  tetrabrom-arsenophenol  are  substances 
structurally  similar  to  arsenophenol,  containing  four  mole- 
cules of  CI  and  Br  in  the  3  and  5  positions  respectively.  As 
compared  with  the  halogen-free  substance,  their  activity  is 
less  marked. 

Dichlorphenylarsenious  acid: 

/O— H 

As=0 
I   \0-H 

/°\ 
HC         CH 

i  I 

CI— C         C— CI 

\c/ 

I 

OH 

This  substance  is  readily  soluble  in  water,  and  can  be  neu- 
tralized with  ease  by  using  a  sodium  carbonate  solution. 
The  dosis  tolerata  for  healthy  mice  is  1  :  75,  whereas  the 
curative  dose  is  1  :  100.  There  is,  therefore,  a  considerable 
margin  of  safety  between  the  tolerant  and  the  curative 
dose,  an  item  that  is  of  the  greatest  importance  in  consider- 
ing the  value  of  any  drug.  A  considerable  drawback  to  its 
use  lies  in  the  fact  that  it  is  capable  of  producing  disturbances 
in  the  nervous  system.  This  in  itself  is  sufficient  to  preclude 
its  use  in  the  treatment  of  spirilloses  or  allied  infections. 
Dioxy-diamino-arseno-benzol  and  its  hydrochloric  acid  salt: 

As===As  As  =As 

/C\  /°\  /°\  /°\ 

HC         CHHC         CH  HC         CH  HC         CH 

NH2C         CHHC         CNH2    C1HNH2C         CHHC         CNH.C1H 
\c/  \c/  \c/  \c/ 

II  II 

OH  OH  OH  OH 

The  first  of  these  substances  was  designated  by  Ehrlich, 
for  purposes  of  brevity,  as  "592."  It  is  a  light-yellow  powder, 
which,  on  account  of  the  property  it  possesses  of  being  very 


HISTORY    AND    DEVELOPMENT    OF    SALVARSAN 


205 


readily  oxidized,  must  be  kept  in  sealed  vacuum  tubes. 
This  substance  is  soluble  in  water  rendered  alkaline  with 
NaOH.  The  hydrochloric  acid  salt  of  this  substance  ("606") 
is  readily  soluble  in  hot  water,  is  strongly  acid,  and  is  ab- 
sorbed with  difficulty  by  the  tissues.  This  latter  peculiarity 
makes  it  unsuitable  for  therapeutic  uses,  at  least  in  its  acid 
form. 

Another  remedy  possessing  great  spirillocidal  power  is 


amidophenylarsenoxid. 
substance  is: 


The    chemical    structure    of    this 


As=0 

I 

/C\ 
H— C         C— H 

I  I 

H— C         C— H 

\c/ 

I 
NH2 

Of  this  substance,  0.03  gm.  is  tolerated  per  kilogram  of  fowl. 
The  quantity  required  to  rid  the  fowl  of  spirilla  is  only  3\> 
of  this  amount,  a  fact  that  makes  this  arsenical  combina- 
tion of  great  therapeutic  significance.  The  comparative 
usefulness  of  the  various  chemical  substances  here  con- 
sidered will  be  seen  from  the  following  table,  showing  the 
dose  tolerated  and  the  dose  required  for  sterilizing  the  fowl: 


Atoxyl 

Arsacetin 

Arsenophenylglycin 

Amidophenylarsenoxid 
Dioxydiamidoarsenobenzol 


Dosis 

TOLERATA. 


0.06 

0.1 

0.4 

0.03 

0.2 


Dosis 
Curattva. 


0.03 

0.03 

0.12 

0.0015 

0.0035 


Proportion. 


*:3 
£:3 


A  glance  at  this  table  shows  that  the  last  two  substances 
possess  the  ideal  qualities  required  of  a  therapeutic  agent, 
and  of  the  two,  the  last  is  the  most  potent. 

The  principle  involved  in  the  conception  of  "chemo- 
therapy" as  elaborated  by  Ehrlich  consists  of  the  finding 
of  a  remedial  agent  that  possesses,  first,  properties  injurious 


206      SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

to  the  "causa  movens"  of  a  given  disease,  and,  second,  one 
that,  when  introduced  into  the  animal  organism,  will  pro- 
duce as  little  disturbance  as  possible.  These  properties  are 
possible  only  after  standardization  and  after  a  careful  con- 
sideration of  the  effects  of  a  given  substance  in  animal 
experimentation. 

The  "chemotherapy"  of  the  past  was  based  more  or  less 
upon  empiricism,  and  embraced  only  a  few  remedial  agents 
whose  properties  were  well  defined.  Mercury  and  the  iodids 
were  regarded  as  specifics  for  syphilis;  quinin,  for  malaria; 
and  later,  atoxyl,  for  sleeping  sickness.  These  substances 
were  utilized  as  the  result  of  experiments  made  in  the  past, 
and  were  not  dependent  upon  the  painstaking  standardiza- 
tion that  characterizes  the  chemical  substances  introduced 
into  therapeutics  by  Ehrlich  and  his  followers.  This  in- 
vestigator differed  from  the  chemists  who  considered  "Cor- 
pora non  agunt,  nisi  fluida,"  and  established  as  a  chemo- 
therapeutic  principle  that  "Corpora  non  agunt,  nisifixata." 
This  conception  is  only  a  part  of  the  original  teaching  of 
Ehrlich  regarding  immune  processes  in  general.  His  theory 
of  immunity  maintains  that  definite  receptors  in  the  body- 
cells  must  be  present  before  a  certain  substance  can  be 
"anchored"  by  the  cell.  In  tetanus,  for  example,  the  cells 
of  the  nervous  system  possess  a  greater  affinity  for  the 
poison  elaborated  by  the  bacterium  than  does  any  other 
body-cell;  this  is  due  to  the  fact  that  they  are  endowed 
with  "receptors,"  which  other  cells  do  not  possess.  When 
arsenic  is  introduced  into  the  body  it  is  fixed  ("anchored") 
by  certain  cell-receptors;  when  mercury  is  introduced,  it 
in  turn  is  fixed  by  other  receptors.  It  is  possible  to  pro- 
duce chemical  substances  that  carry  side-chains  that  are 
capable  of  being  fixed  by  certain  cells  only  or  by  certain 
bacteria  if  need  be. 

It  was  the  original  intention  of  Ehrlich  to  produce  a  sub- 
stance that  would  carry  in  its  complex  makeup  a  molecule 
or  a  group  of  molecules  that  would  be  anchored  by  the 
invading  microorganism  to  a  much  greater  extent  than  by 
the  body-cells  of  the  infected  animal.  Thus  when  the  micro- 
organism fixes  (anchors)  the  given  molecule,  it  also  carries 


HISTORY   AND   DEVELOPMENT   OF   SALVARSAN         207 

with  it  the  remainder  of  the  chemical  substance,  whatever 
that  may  be;  at  the  same  time,  the  side-chain  that  is  an- 
chored or  is  responsible  for  the  anchoring  of  the  entire  mole- 
cule need  not  possess  any  of  the  properties  of  the  entire  mole- 
cule or  of  any  part  thereof.  For  example,  when  the  molecule 
of  "606"  is  anchored  to  the  treponema  of  syphilis  by  its  OH 
or  its  NH2  side-chain,  or  by  both,  it  must  later  contend 
with  two  molecules  of  arsenic,  which,  being  in  a  trivalent 
condition,  can  exercise  to  a  marked  degree  its  toxic  effects  on 
the  microorganisms.  The  side-chains  as  they  exist  in 
"606"  are  much  more  readily  taken  up  by  the  Treponema 
pallidum  than  by  the  body-cells,  as  is  shown  by  the  dosis 
tolerata  as  compared  with  the  dosis  curativa. 

The  chief  point  to  be  observed  in  the  introduction  of 
chemicals  into  a  living  organism  is  that  the  infective  agent 
will  fix  the  given  drug,  and,  as  a  result  of  this  fixation,  it  will 
die,  or,  as  is  the  case  with  some  chemicals,  reproduction  will 
be  inhibited.  This  quality  was  established  in  the  production 
of  dioxydiamidoarsenobenzol,  in  that  it  is  fixed  by  its  amido- 
oxy-group  (haptophore  group  of  the  molecule)  by  the  Tre- 
ponema pallidum,  which  is  killed  by  receiving  the  molecule 
in  its  economy,  a  fact  that  was  demonstrated  by  animal 
experimentation  as  well  as  by  clinical  observations. 

From  the  encouraging  clinical  reports  received  as  the 
result  of  experiments  carried  out  on  many  thousands  of 
cases  and  on  animals  before  the  drug  was  placed  in  the 
hands  of  the  general  medical  profession,  Ehrlich  believed 
at  the  time  that  in  the  "606"  molecule  he  had  discovered  a 
means  of  ridding,  by  a  single  administration,  the  human 
organism  of  the  cause  of  syphilis.  This  conception  of  a 
"Therapia  sterilisans  magna,"  although  established  in  indi- 
vidual cases,  did  not  wholly  come  up  to  the  expectations 
of  this  eminent  investigator. 

Syphilis  cannot  be  cured  with  one  injection  of  salvarsan, 
and  the  physician  who  attempts  to  assert  definitely  how 
many  injections  are  required  is  merely  doing  so  as  the  result 
of  conjecture,  as  there  are  no  standards  as  yet  that  would 
establish  the  number  of  treatments  required  in  a  given  case 
of  syphilis. 


208      SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

In  many  instances  the  reports  showed  that  it  is  not  an 
altogether  easy  task  to  prepare  the  substance  for  injection, 
and  that  some  chemical  preparation  that  would  require  less 
handling  would  be  most  acceptable.  With  this  end  in  view, 
Ehrlich  resumed  his  search  for  a  more  ideal  substance,  and 
as  the  result  of  his  nine  hundred  and  fourteenth  experi- 
ment he  gave  us  neosalvarsan  ("914").  This  substance  is  a 
definite  mixture  of  sodium-3  diamino-4  dihydroxy-1  arseno- 
benzene  methanal  sulphoxalate  (according  to  the  New  and 
Non-official  Remedies,  Jour.  Amer.  Med.  Assoc,  1913).  The 
chemical  formula  may  be  represented  as  follows: 

As-  =As 


/c\ 

H— C         C— H 

H— C         C— H 

H— C         C— NH2 

H— C         C— NH(CH20)OSNa 

OH  OH 

This  substance  contains  in  three  parts  by  weight  ap- 
proximately the  same  amount  of  arsenic  contained  in  two 
parts  by  weight  of  salvarsan.  Salvarsan  and  neosalvarsan 
are  dispensed  in  sealed  tubes,  containing  varying  quantities. 
Neosalvarsan  may  be  obtained  in  tubes  containing  from 
0.15  to  0.9  gm.  Salvarsan  may  be  had  in  amounts  up  to 
0.6  gm.,  which  represents  the  full  dose  usually  given  to 
adults.  The  ampules  of  salvarsan  are  filled  with  an  indiffer- 
ent gas,  such  as  N,  in  order  to  obviate  chemical  changes. 
It  must  be  remembered  that  salvarsan  is  readily  decom- 
posed, forming  substances  of  a  toxic  nature,  and  must  con- 
sequently be  used  as  soon  as  an  ampule  is  opened,  not  per- 
mitting it  to  remain  in  too  prolonged  contact  with  air. 
It  is  best  to  prepare  the  solution  at  the  bedside  and  use  it 
at  once. 

The  following  extract  concerning  the  properties  of  these 
two  drugs  is  taken  from  the  Journal  of  the  American  Medical 
Association: 

Salvarsan  contains  31 .57  per  cent,  of  arsenic.  It  is  a  yellow, 
crystalline,  hygroscopic  powder,  very  unstable  in  air.     It 


HISTORY    AND   DEVELOPMENT    OF   SALVARSAN         209 

is  readily  soluble  in  water,  particularly  when  hot,  yielding  a 
solution  with  an  acid  reaction.  The  addition  of  sodium 
hydroxid  solution  to  an  aqueous  solution  of  salvarsan,  in 
the  ratio  of  two  molecules  of  sodium  hydroxid  to  one  of 
salvarsan,  precipitates  the  free  base,  namely,  (NH2OH,- 
C6H3As  :  As,C6H3OH,NH2).  On  the  addition  of  an  aqueous 
solution  of  sodium  carbonate  to  an  aqueous  solution  of 
salvarsan  a  precipitate  is  produced  which  is  insoluble  in  an 
excess  of  the  reagent.  An  aqueous  solution  of  salvarsan  is 
not  affected  by  the  addition  of  dilute  hydrochloric,  nitric,  or 
sulphuric  acids. 

When  salvarsan  is  heated  with  an  alkaline  solution  of 
potassium  permanganate,  the  permanganate  solution  is 
reduced  and  ammonia  is  given  off.  The  addition  of  ferric 
chlorid  solution  to  an  aqueous  solution  of  salvarsan  pro- 
duces a  brownish-violet  color,  which  gradually  changes  to  a 
dark  red;  finally  the  liquid  becomes  turbid. 

Silver  nitrate  solution  added  to  an  aqueous  solution  of 
salvarsan  acidified  with  dilute  nitric  acid  yields  a  dark- 
yellow  precipitate  which  rapidly  becomes  black. 

The  addition  of  concentrated  nitric  acid  to  an  aqueous 
solution  of  salvarsan  produces  a  yellowish-white  precipitate. 
On  further  addition  of  the  acid  the  precipitate  redissolves 
and  the  solution  becomes  dark  red. 

Neosalvarsan  is  an  orange-yellow  powder  possessing  a 
peculiar  odor.  It  is  very  unstable  in  the  air.  It  is  readily 
soluble  in  water,  yielding  a  yellow  solution  which  is  neutral 
toward  litmus.  Upon  standing  the  aqueous  solution  be- 
comes dark  brown,  forming  a  brown  precipitate. 

A  freshly  prepared  aqueous  solution  of  neosalvarsan 
(1  :  100)  yields  a  precipitate  on  the  addition  of  mineral  acids. 

If  silver  nitrate  test  solution  be  added  to  an  aqueous  solu- 
tion of  neosalvarsan  (1  :  100),  a  brownish  color  should  be 
produced,  quickly  followed  by  the  formation  of  a  black  pre- 
cipitate. 

If  ferric  chlorid.  test  solution  be  added  to  an  aqueous 
solution  of  neosalvarsan  (1  :  100),  a  violet  color  should  be 
produced,  which  soon  changes  to  a  dark  red. 

If  to  10  c.c.  of  an  aqueous  solution  of  neosalvarsan  (1  :  100) 

14 


210      SEROLOGY  OF   NERVOUS    AND   MENTAL    DISEASES 

5  c.c.  of  dilute  hydrochloric  acid  be  added  and  the  mixture 
heated,  the  irritating  odor  of  sulphur  dioxid  will  be  evolved. 
If  to  10  c.c.  of  the  aqueous  solution  of  neosalvarsan 
(1  :  100)  5  c.c.  of  diluted  hydrochloric  acid  be  added,  the  pre- 
cipitate collected  on  a  filter  and  treated  with  zinc  dust  and 
warm,  diluted  hydrochloric  acid  in  a  test-tube,  and  if  paper 
moistened  with  a  5  per  cent,  cadmium  chlorid  solution  be 
held  in  the  mouth  of  the  tube,  the  paper  should  be  stained 
yellow  within  a  few  minutes.     (Distinction  from  salvarsan.) 

EARLY  METHODS  AND  RESULTS 

Because  of  the  marked  instability  of  salvarsan  and  neo- 
salvarsan, it  is  well  to  see  that  the  ampule  containing  the 
drug  is  intact,  and  that  the  powder  is  of  a  yellow,  and  not  of 
a  gray  or  brownish,  color.  Any  drug  not  up  to  this  standard 
must  be  regarded  as  deteriorated,  and  hence  dangerous  for 
therapeutic  purposes. 

In  the  early  methods  only  salvarsan  was  used,  the  drug 
being  given  intramuscularly,  subcutaneously,  and  intra- 
venously. For  the  muscular  and  subcutaneous  injections 
acid  solutions,  alkaline  solutions,  neutral  emulsions,  and 
paraffin  mixtures  were  employed.  These  various  methods 
of  giving  the  drug  will  now  be  considered  briefly  and  in  order: 

The  Acid  Solution. — The  equipment  necessary  for  the 
preparation  of  the  acid  solution  consists  of  a  25  c.c.  graduated 
cylinder  with  a  ground-glass  stopper.  This  cylinder  con- 
tains a  number  of  medium-sized  glass  beads,  about  30  in  all. 
A  small  25  c.c.  griffin-lip  beaker  with  a  cotton  plug,  and, 
lastly,  distilled  water,  are  also  required.  These  must  all  be 
sterile  before  using. 

For  intramuscular  injection  the  drug  is  prepared  as  fol- 
lows: Having  placed  the  salvarsan  in  the  cylinder,  add  at 
once  boiling  sterile  distilled  water  and  shake  vigorously. 
The  drug  dissolves  readily,  a  yellow  fluid  resulting.  Pour 
the  fluid  into  the  beaker,  and  it  is  ready  for  injection. 

This  form  of  treatment  was  usually  followed  by  intense 
local  reactions,  and  for  this  reason  is  not  to  be  recommended. 

The  Alkaline  Solution  (Alt). — The  equipment  for  the 
preparation  of  this  solution  is  similar  to  that  used  above, 


EARLY  METHODS   AND   RESULTS  211 

with  the  addition  of  a  4  per  cent,  sodium  hydroxid  solution, 
an  additional  graduated  cylinder  of  25  c.c.  capacity,  and  a 
graduated  1  or  2  c.c.  pipet.  Everything  used  must  be 
sterile. 

First  prepare  an  acid  solution  as  previously  directed.  To 
this  add  0.5  c.c.  of  the  sodium  hydroxid  solution  for  every 
0.1  gm.  of  the  drug.  Shake  vigorously.  This  produces  a 
yellowish,  at  times  a  brownish,  opaque  fluid;  to  this  add 
the  alkali  drop  by  drop  until  the  opacity  vanishes.  It  is  not 
advisable  that  an  absolutely  clear  solution  be  produced 
by  the  addition  of  more  alkali,  as  the  slightly  opaque  fluid 
is  less  irritating  than  a  very  clear  fluid  would  be.  This 
alkaline  solution  is  also  used  for  intramuscular  injections, 
as  suggested  by  Alt.  This  mode  of  administering  salvarsan 
is  less  irritating  than  the  injection  of  an  acid  solution. 

The  Neutral  Emulsion  (Michaelis). — The  same  utensils  are 
required  here  as  in  preparing  the  alkaline  salvarsan,  and,  in 
addition,  a  bottle  containing  1  per  cent,  acetic  acid  solution 
and  another  containing  0.5  per  cent,  solution  of  phenol- 
phthalein  in  70  per  cent,  alcohol  are  also  necessary.  Every- 
thing used  must  be  sterile. 

The  first  step  consists  in  preparing  a  perfectly  clear 
alkaline  solution,  as  previously  described;  add  two  or  three 
drops  of  the  phenolphthalein  solution;  this  results  in  a  red 
coloration  of  the  fluid;  finally  add,  drop  by  drop,  1  per  cent, 
acetic  acid  solution.  The  salvarsan  is  precipitated  as  very 
fine,  yellowish  flocculi,  and  the  acetic  acid  is  added  until  all 
traces  of  pink  color  disappear  from  the  mixture.  The  emul- 
sion is  poured  into  the  beaker,  and  the  cylinder  is  rinsed  with 
a  little  distilled  water  and  this  added  to  the  contents  of  the 
beaker.  The  emulsion  is  now  ready  for  use,  either  subcu- 
taneously  or  intramuscularly. 

Neutral  Emulsion  (Wechselmann). — Apparatus  required: 
Mortar  and  pestle;  15  per  cent.  NaOH  solution;  glacial  acetic 
acid;  tV  normal  NaOH  solution;  1  per  cent,  acetic  acid;  red 
and  blue  litmus-paper;  a  platinum  loop;  a  small  centrifuge 
with  sterile  centrifuge  tubes;  sterile  physiologic  salt  solution; 
sterile  distilled  water.  The  salvarsan  is  rubbed  up  in  the 
mortar  with  1  or  2  c.c.  of  the  15  per  cent.  NaOH  solution, 


212      SEROLOGY   OF   NERVOUS    AND   MENTAL    DISEASES 

which  dissolves  it.  Glacial  acetic  acid  is  added  a  drop  at  a 
time,  which  results  in  the  formation  of  a  glutinous  yellow 
mass  that  is  diluted  with  1  or  2  c.c.  of  sterile  distilled  water, 
and  carefully  neutralized  with  the  decinormal  NaOH  solu- 
tion, using  the  platinum  loop  for  transferring  a  drop  to  the 
litmus-paper.  This  causes  the  formation  of  sodium  acetate, 
which  must  be  removed  before  the  emulsion  is  ready  for  use. 
The  centrifuge  serves  the  purpose  of  showing  that  the  neutral 
salvarsan  in  the  centrifugalized  fluid  is  at  the  bottom  of  the 
tube,  the  clear  fluid  on  top  representing  the  sodium  acetate; 
this  last  is  poured  off  and  discarded.  The  remaining  salvar- 
san at  the  bottom  of  the  centrifuge  tubes  is  taken  up  with 
from  4  to  6  c.c.  of  sterile  water,  and  the  emulsion  is  ready  for 
use,  either  subcutaneously  or  intramuscularly. 

All  the  methods  here  outlined  of  administering  the  drug 
have  the  peculiarity  of  producing  in  a  few  days  painful 
swellings,  and  at  times  quite  extensive  infiltrations  and 
necroses  take  place.  The  subcutaneous  and  intramuscular 
methods  are  not  to  be  recommended,  as  by  the  intravenous 
administration  of  the  drug  all  local  manifestations  that  are 
encountered  by  the  other  methods  described  are  avoided. 

Oil  and  Paraffin  Mixtures. — It  has  been  demonstrated 
that  these  mixtures,  when  kept  in  dark  containers,  do  not 
deteriorate  for  some  time.  This  cannot,  however,  be  de- 
pended upon,  as  the  slightest  decomposition  of  the  original 
salvarsan  is  capable  of  producing  marked  toxic  manifesta- 
tions. It  is,  therefore,  best  to  prepare  the  drug  immediately 
prior  to  use,  and  not  to  utilize  any  drug  that  is  left  from  a 
previous  preparation. 

In  preparing  these  mixtures  salvarsan  is  rubbed  up  in 
a  mortar  with  some  one  of  the  following  substances:  Liquid 
paraffin,  the  finest  sterile  olive  oil,  oil  of  sesame,  or  sterilized 
liquid  vaselin.  The  quantity  of  any  one  of  these  sub- 
stances is  measured,  so  that  1  c.c.  of  the  oil  or  paraffin  is 
added  to  each  0.1  c.c.  of  the  drug.  This  mixture  may  be  in- 
jected in  toto,  or,  as  Kromayer  suggests,  0.1  to  0.2  of  the 
drug  (1  or  2  c.c.  of  the  mixture)  may  be  injected  every 
second  day.  When  the  latter  method  is  to  be  employed, 
the  drug  must  be  kept  in  a  sterile  dark  bottle.    Before  using 


Fig.  20. 


-Necrosis  resulting  from    an    intramuscular    injection    of 
neutral  solution  of  salvarsan. 


INJECTION    OF   THE    DRUG  213 

it,  the  drug  must  be  rubbed  up  thoroughly,  as  a  heavy 
sediment  collects  at  the  bottom  of  the  flask. 

Although  the  injection  in  itself  is  painless,  a  few  days 
after  the  treatment  sensitive  infiltrations  develop  that 
will  at  times  persist  for  weeks. 

DOSAGE 

Males  receive  in  general  about  0.6  gm.,  whereas  female  pa- 
tients are  given  0.5  gm.  of  salvarsan.  This  dosage  is  the  same 
whether  the  mixture  be  acid,  alkaline  or  neutral,  or  oil  or  par- 
affin. Weak  patients  with  organic  diseases  of  a  grave  nature 
should  receive  smaller  doses — 0.3  or  0.4  gm.  of  salvarsan. 

For  infants  suffering  from  congenital  syphilis  the  dose  is 
from  6  to  10  milligrams  of  salvarsan  for  every  kilogram  of 
body-weight,  so  that  a  child  weighing  4  kilograms  would 
receive  from  0.024  to  0.04  gm.  of  salvarsan.  To  older 
children,  weighing  from  20  to  30  kilograms,  1  centigram  of 
the  drug  is  given  for  every  kilogram  of  body-weight. 

INJECTION  OF  THE  DRUG 

For  the  oil  and  paraffin  emulsions  it  is  best  to  use  a  syringe 
with  an  asbestos  plunger;  for  the  watery  mixtures  an  ordinary 
Record  syringe  will  suffice.  The  substance  is  injected 
through  a  cannula,  care  being  exercised  that  the  cannula 
does  not  injure  a  blood-vessel.  This  may  be  accomplished 
by  introducing  the  cannula  without  the  syringe  attach- 
ment, and  turning  it  around  a  few  times  to  be  certain  that 
no  blood-vessel  is  near.  Having  taken  this  precaution,  the 
substance  may  now  be  very  slowly  injected.  The  best  site 
for  making  the  injection  is  in  the  gluteal  region.  The  small 
of  the  back  (erector  spina?  group  of  muscles)  is  also  an  ex- 
cellent injection  area,  as  absorption  from  this  region  is  very 
rapid.  After  receiving  the  injection,  it  is  well  to  keep  the 
patient  in  bed  for  a  few  days. 

The  Intravenous  Injection. — The  advocates  of  the  intra- 
muscular or  subcutaneous  route  belong  to  the  early  days  of 
the  use  of  salvarsan,  when  the  conception  of  a  "therapia 
sterilisans  magna"  still  prevailed,  and  the  belief  existed  that 
this  could  be  accomplished  with  one  or  two  injections  of  the 


214      SEROLOGY   OP    NERVOUS   AND    MENTAL   DISEASES 

drug.  The  enormous  number  of  applications  of  salvarsan 
that  were  made  quickly  dispelled  the  belief  that  a  cure 
would  follow  one  or  two  injections,  and  hence  the  intra- 
muscular and  subcutaneous  methods  were  discarded  on 
account  of  the  unpleasant  local  manifestations  that  resulted. 
The  comparatively  easy  technic  of  the  intramuscular  method 
made  this  form  of  administration  popular  with  those  who 
were  not  acquainted  with  the  manipulation  of  veins,  or  who 
had  had  unfortunate  experiences  with  attempted  intra- 
venous injections.  As  a  result,  some  physicians  effected 
a  compromise,  and  advised  the  use  of  both  methods,  giving 
one  intramuscular  and  later  an  intravenous  injection  of  the 
drug.  This  combined  method  was  said  by  some  to  have 
great  possibilities. 

The  wide  notice  the  drug  received  resulted  in  attempts 
to  use  salvarsan  in  every  possible  way,  and  today,  after  more 
than  five  million  doses  of  this  remedy  have  been  disposed 
of,  the  intravenous  method  holds  first  place  in  efficiency, 
safety,  and,  with  some  practice,  ease  of  administration. 
Further  on  certain  methods  will  be  described  that  tend  to 
increase  the  efficiency  of  the  drug  by  injecting  it  in  the  par- 
ticular part  affected;  a  method  will  also  be  given  that  tends 
to  establish  a  form  of  fractional  sterilization. 

The  best  manner  of  using  salvarsan  is  an  attainment  to  be 
achieved  by  future  therapeutists,  when  more  factors  will 
enter  into  the  method  of  using  the  drug.  This  particular 
sphere  of  activity  confronts  the  neurologist,  who  is  guided 
by  clinical  as  well  as  by  important  laboratory  data  as  to  the 
progress  of  treatment. 

The  intravenous  method  held  out  much  more  hope  for  the 
ultimate  realization  of  Ehrlich's  conception  of  a  "therapia 
sterilisans  magna,"  but  that  this  will  be  the  result  not  of  one 
but  of  many  injections  is  also  a  well-established  fact.  In  the 
intravenous  method  of  administering  salvarsan  we  possess  the 
key  to  the  entire  therapeutic  structure  of  syphilitic  therapy, 
which,  it  is  hoped,  will  be  accomplished  in  the  near  future. 

The  following  description  shows  in  detail  the  instruments 
required,  the  preparation  of  salvarsan  and  of  neosalvarsan, 
and  the  preparation  of  the  patient  for  receiving  the  injection. 


Fig.  21. — The  Weintraud-Assmy  intravenous  apparatus. 


INJECTION  OF   THE   DRUG  215 

Instruments  Required  for  Intravenous  Injection. — As  a 
general  precautionary  measure  it  should  be  remembered 
that  anything  used  in  the  preparation  of  salvarsan  must  be 
scrupulously  clean  and  sterile.  It  will,  therefore,  be  stated 
at  the  beginning,  and  repeated  further  on,  that  after  having 
been  used  the  entire  apparatus  is  to  be  cleansed  at  once — 
needle,  container,  rubber  tubing,  etc.  It  is  a  generally 
accepted  fact  that  the  fewer  the  parts  of  an  apparatus  and 
the  simpler  its  working  mechanism,  the  better  suited  it  is 
for  use.  This  applies  especially  to  the  salvarsan  outfit. 
Occasionally  some  worker  will  prefer  an  apparatus  to  which 
he  has  become  accustomed,  and  which  would  require  much 
time  for  one  to  learn  if  he  had  never  used  that  particular 
apparatus  before.  In  these  cases  it  is  useless  to  advise  the 
purchase  of  a  new  outfit.  The  description  that  follows 
embraces  general  principles,  and  shows  the  apparatus  the 
author  considers  of  most  value  because  of  simplicity  and 
ease  of  handling. 

The  instruments  to  be  used  may  be  divided  into  those  that 
are  required  for  dissolving  the  drug  and  those  employed  for 
the  injection  of  the  solution.  Mortars  and  pestles  are  not 
necessary  for  the  intravenous  method.  The  drug  may  be 
dissolved  in  a  350  c.c.  graduated,  glass-stoppered  cylinder, 
and  poured  from  this  into  the  injecting  apparatus  when 
ready  for  use.  For  the  injection  of  the  solution  any  ap- 
paratus the  physician  is  accustomed  to  use  will  answer,  pro- 
vided it  has  an  attachment  that  will  permit  of  the  inter- 
ruption of  the  salvarsan  flow  and  the  substitution  of  normal 
sterile  salt  solution.  The  reason  for  this  will  be  discussed 
later,  under  the  head  of  Symptoms  Accompanying  the 
Injection.  An  apparatus  that  possesses  all  the  advantages 
is  seen  in  the  Weintraud-Assmy  outfit,  which  consists  of: 

One  buret  holder. 

One  holder  for  two  graduated  cylinders  (nickeled). 

Two  graduated  cylinders  of  200  c.c.  capacity. 

Rubber  tube  leading  from  each  cylinder. 

Two  glass  connecting  pieces. 

One  nickeled  two-way  cock. 

A  steel  needle  with  point  beveled  obtusely. 


216      SEROLOGY    OF   NERVOUS   AND   MENTAL   DISEASES 


In  the  author's  work  the  following  apparatus  was  used, 
which  is  a  slight  modification  of  the  one  employed  at  the 
Rockefeller  Institute  Hospital;   it   consists  of  a  400   c.c. 


Fig.  22. — Author's  apparatus  assembled  and  ready  for  use. 

cylinder,  provided  with  two  rubber  stoppers,  one  solid  and 
the  other  having  two  perforations.  The  stopper  with  the 
perforations  has  one  short  glass  tube  and  one  long  one, 


Fig.  23. — The  apparatus  used  by  the  author.  From  left  to  right,  long 
air  tube  and  near  it  the  short  salvarsan  tube;  the  carbon  filter  for  the 
salt  solution;  the  needle;  the  cylinder  and  rubber  stopper.  At  the 
bottom  the  three-way  cock  and  delivery  glass  tube. 


INJECTION    OF   THE    DRUG  217 

as  may  be  seen  in  the  illustration  (Fig.  23).  The  short 
glass  tube  has  a  rubber  attachment  connected  with  a  three- 
way  cock  through  an  intermediary  glass  connecting  tube. 
A  50  c.c.  carbon  filter  is  seen  at  the  right  of  the  long  tube, 
which  is  also  provided  with  a  rubber  tube  that  runs  to  the 
three-way  cock.  To  the  free  end  of  the  three-way  cock  is 
attached  a  piece  of  rubber  carrying  a  delivery  tube.  All 
rubber-glass  and  rubber-metal  connections  are  securely 
tied  with  cord  or  silk  to  prevent  slipping  or  leakage. 
Two  rubber  bands — a  large  and  a  small  one — prevent 
the  accidental  falling  out  of  the  rubber  stopper  when 
the  apparatus  is  filled  with  the  solution  and  turned 
over.  The  advantage  of  this  contrivance  lies  in  the  fact 
that  it  eliminates  the  need  for  a  separate  mixing  vessel,  the 
drug  being  mixed  in  the  same  cylinder  from  which  it  is 
delivered.  Having  dissolved  the  drug  and  shaken  it,  the 
solid  stopper  is  replaced  by  the  perforated  one,  and  secured 
with  the  larger  rubber  band;  the  apparatus  is  now  turned 
over,  having  turned  the  three-way  cock  so  that  it  will 
deliver  from  the  carbon  filter  only.  The  outfit  is  suspended 
by  the  attached  tape  and  the  carbon  filter  adjusted,  secur- 
ing it  to  the  side  of  the  cylinder  by  means  of  the  smaller 
rubber  band.  Saline  solution  is  poured  into  the  carbon 
filter,  and  the  air  expelled  by  lowering  the  delivery  tube. 
The  procedure  of  expelling  the  air  is  to  be  repeated,  having 
turned  the  cock  so  that  it  will  deliver  salvarsan,  the  air  con- 
tained in  the  rubber  tubing  also  being  expelled.  Before 
using,  the  cock  must  be  directed  to  the  saline  delivery,  as 
it  is  advisable  to  begin  with  the  saline,  and  have  the  glass 
connecting  tube  filled  flush  to  the  tip  with  the  salt  solution. 

Special  instruction  must  be  given  regarding  the  use  of  the 
needle.  The  author  does  not  recommend  the  use  of  the 
Schreiber  needle  or  of  any  but  an  ordinary  straight  needle, 
and  cautions  against  using  those  possessing  special  curves, 
cumbersome  attachments,  too  wide  a  lumen,  or  a  special 
stilet  and  cannula.  It  is  safest  to  grow  accustomed  to 
manipulating  the  simplest  needle,  such  as  the  one  shown  in 
the  illustration  of  the  salvarsan  outfit  (Fig.  22).  This  is  an 
ordinary  Yale-Luer  needle,  with  a  No.  19  bore,  and  is  \\ 


218      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

inches  long.  These  needles  are  very  serviceable,  cheap,  and 
a  dozen  can  be  used  for  months,  even  where  many  injections 
are  given  daily. 

The  other  apparatus  shown  in  Fig.  24,  the  Fox-Trimble, 
does  not  meet  the  requirements  on  account  of  the  absence  of 
an  attachment  for  the  salt  solution.  The  same  may  be  said 
of    the   Iversen-Wolbarst  outfit   (Fig.  25),  which  has  the 


Fig.  24. — The  Howard  Fox  and  W.  B.  Trimble  apparatus  for  the 
intravenous  injection  of  salvarsan.  The  Schreiber  needle  is  shown  at  the 
bottom  of  the  cut. 


additional  disadvantage  that  it  requires  an  air-bulb,  driving 
the  solution  into  the  vein. 

Besides  the  delivery  apparatus,  the  tourniquet  may  be 
included  as  a  part  of  the  salvarsan  injecting  outfit.  This 
need  not  be  an  elaborate  affair,  and  the  artery  clamp  may  be 
eliminated.  With  a  little  practice  one  can  learn  how  to  apply 
the  tourniquet,  which  consists  of  an  ordinary  piece  of  irriga- 
tion tubing,  and  be  able  to  ascertain  at  a  glance  whether  or 
not  it  is  too  tight.     An  extra  supply  of  needles  should  be 


PREPARATION  OF  SALVARSAN  219 

carried  in  case  of  emergency,  and  more  saline  solution  than 
is  required  for  one  treatment  should  also  be  at  hand.    The 


Fig.    25. — The    Iversen-Wolbarst    intravenous    salvarsan    apparatus. 
The  Schreiber  needle  is  not  part  of  the  outfit. 

additional   equipment   consists   of   a   rubber   sheet,    sterile 
gauze  pads,  towels,  alcohol,  ether,  and  collodion. 

PREPARATION  OF  SALVARSAN 

An  important  requisite  is  the  employment  of  freshly  dis- 
tilled sterile  water  in  preparing  the  solution  of  salvarsan 
for  intravenous  use.  In  order  to  have  this  at  hand  a  water 
still  is  indispensable.  It  must  be  remembered  that  unless 
this  rule  is  rigorously  adhered  to,  satisfactory  results  cannot 
be  expected.  A  very  simple  still  can  be  installed  in  a  phys- 
ician's office  near  a  water  faucet  and  a  sink,  and  enough 
water  can  be  had  for  a  dozen  salvarsan  injections  if  need  be. 


220      SEROLOGY  OF    NERVOUS    AND    MENTAL    DISEASES 


Such  a  water  still  is  shown  in  Fig.  26,  and,  from  the  author's 
experience,  is  a  very  satisfactory  and  inexpensive  apparatus. 
Having  secured  enough  distilled  water,  350  c.c.  are  next 
placed  in  an  Erlenmeyer  flask  of  500  c.c.  capacity,  and 
boiled  for  five  minutes.  This  is  sufficient  to  render  the  water 
sterile  for  use  with  salvarsan.  While  still  very  hot,  100  c.c. 
of  the  water  is  placed  in  the  container.  (See  p.  215.)  The 
ampule  of  salvarsan  is  meanwhile  kept  in  95  per  cent,  alcohol 
to  sterilize  the  surface  of  the  container;  the  file  is  also  placed 


Fig.  26. — Muencke's  distilling  apparatus  for  office  use.     The  cut  does 
not  show  the  Bunsen  burner. 

in  the  same  fluid.  After  removing  the  ampule  from  the  alco- 
hol and  drying  it,  with  a  firm  pressure  against  the  glass  with 
the  file  rasp  the  neck  and  break  it  off  by  striking  the  tip 
firmly.  Pour  the  contents  into  the  container  with  the  hot 
sterile  distilled  water,  close  tightly  with  the  rubber  stopper, 
and  shake  the  contents  until  every  trace  of  undissolved 
drug  is  gone.  This  sometimes  requires  from  one-half  to  one 
minute's  shaking.  The  next  step  is  to  neutralize  the  di- 
chlorhydrate  salt,  which  is  accomplished  by  the  gradual 
addition  (drop  by  drop)  of  a  15  per  cent.  NaOH  solution. 


PREPARATION  OF  SALVARSAN  221 

This  step  must  be  carried  out  with  precision,  as  too  alkaline 
or  insufficiently  neutralized  solutions  are  harmful.  After 
thorough  shaking  and  inspection  of  the  delivery  cylinder 
to  ascertain  that  no  particles  of  undissolved  drug  are  ad- 
hering to  the  cylinder  wall,  the  15  per  cent.  NaOH  solution 
is  poured  into  the  cylinder  drop  by  drop  until  about  11 
or  12  drops  have  been  instilled.  Having  replaced  the 
rubber  stopper,  shake  the  contents  vigorously.  This  addi- 
tion of  the  alkali  forms  the  mono-acid  product,  which  is  still 
in  a  state  of  solution.  The  reaction  that  takes  place  is  as 
follows : 

NH2(C1H)  NH2 

C6H^OH  C6H3^OH 

||    +  H20  +  NaOH      .  ||    +  NaCl  +  H20 

As  As 

C6H3ZoH  C6H  ^OH 

XNH2(C1H)  XNH2(C1H) 

The  futher  addition  of  NaOH  to  the  foregoing  solution 
produces  the  neutral  suspension  by  neutralizing  the  other 
C1H  molecule.  The  addition  of  a  few  more  drops  produces 
the  alkaline  suspension,  which  has  the  following  formula: 

NH2 

C6H3^OH— (NaOH) 

As 

II 
As 

C6H3ZoH 

XNH_, 

On  adding  a  few  drops  more, — usually  up  to  16  or  19, — the 
suspension  clears  up,  when  the  solution  is  ready  for  use;  its 
formula  is  as  follows: 

NH2 
C6h/0H— (NaOH) 


As 

II 

As 


c6h/oh- 


NH2 


222      SEROLOGY   OF    NERVOUS    AND    MENTAL   DISEASES 

The  drug  was  utilized  in  every  one  of  the  foregoing  for- 
mulae. We  know  today  that  the  only  safe  and  least  irritating 
preparation  is  the  slightly  alkaline  solution.  The  subcu- 
taneous and  the  intramuscular  methods  are  far  less  effective 
than  the  intravenous,  and  the  physician  who  does  not 
employ  the  last-named  method  cannot  be  said  to  have 
used  the  drug  in  its  most  potent  therapeutic  form;  neither 
is  he  justified  in  criticizing  the  drug  because  of  certain 
failures  that  he  may  have  experienced,  as  his  method  of 
using  the  drug  was  not  the  one  capable  of  accomplishing  the 
greatest  good  for  the  patient. 

The  Preparation  of  Reosalvarsan. — This  powder  is  much 
more  readily  dissolved  than  the  older  salvarsan.  Place  the 
drug  in  a  container,  and  for  the  full  dose — i.  e.,  0.9  gm. — add 
about  175  to  200  c.c.  of  water  of  the  same  quality  as  was 
used  in  the  preparation  of  salvarsan.  The  drug  dissolves 
and  leaves  a  clear  solution,  when  it  is  ready  for  use.  The 
water  used  for  the  solution  must  be  cold,  as  hot  water  de- 
composes the  drug  and  renders  it  toxic.  No  neutralization 
is  required,  a  fact  that  makes  it  a  very  acceptable  prepara- 
tion for  those  who  do  not  possess  the  required  technic  for 
handling  glass  apparatus  and  chemicals.  Neosalvarsan  can 
also  be  given  in  concentrated  form  through  an  ordinary 
large  Luer  syringe  by  dissolving  the  substance  in  20  c.c.  of 
sterile  distilled  water  and  injecting  it  into  the  vein. 

PREPARATION  OF  THE  PATIENT  FOR  INJECTION 

Although  in  the  great  majority  of  instances  no  special 
preparation  of  the  patient  is  necessary,  it  is,  nevertheless, 
best  to  administer  the  drug  on  an  empty  stomach.  Having 
instructed  the  patient  to  refrain  from  luncheon,  the  drug 
is  injected  in  the  evening,  before  bedtime.  It  is  also  well 
to  direct  the  patient  to  empty  his  bowels  some  time  before 
the  contemplated  treatment, — say,  the  night  before, — so 
that  no  toxic  substances  may  be  absorbed  from  the  gut  and 
give  rise  to  unpleasant  complications.  When  proper  pre- 
cautions are  observed  in  administering  the  remedy,  its  use  has 
proved  to  be  so  free  from  untoward  manifestations  that  many 
physicians  now  inject  it  without  any  preparation  whatever. 

For  the  last  two  years,  since  the  method  of  using  salvarsan 


THE  TECHNIC   OF   INJECTION  223 

and  the  general  information  regarding  the  drug  have  been 
placed  on  a  surer  footing,  the  author  has  not  observed  a 
single  grave  complication.  In  using  the  drug  the  peculiari- 
ties of  the  remedy  and  the  patient's  condition  as  well  must 
be  considered.  It  is  bad  practice  to  administer  a  small  dose 
at  prolonged  intervals  to  a  patient  with  active  cerebral  lues, 
as  this  is  very  often  the  cause  of  a  neuro-recidive  or  a  Herx- 
heimer,  and  it  is  just  as  bad  to  administer  a  perivenous  in- 
filtration, an  insufficiently  neutralized  solution,  or  a  too 
strongly  alkaline  solution.  Whenever  possible,  it  is  best  for 
the  patient  to  be  in  bed  when  the  treatment  is  given;  an 
operating-room  is  entirely  unnecessary. 

THE  TECHNIC  OF  INJECTION 
Where  the  administration  of  salvarsan  or  of  neosalvarsan 
is  a  routine  practice,  the  injection  of  these  remedies  does 
not  rise  above  the  dignity  of  a  hypodermoclysis.  To  those 
who  use  the  drug  very  infrequently,  however,  the  injection 
will  prove  an  operation  of  considerable  difficulty.  Some 
therapeutists  with  considerable  experience  in  making  the 
intravenous  injection  declare  that  the  method  of  introducing 
the  needle  in  injecting  salvarsan  is  precisely  the  same  as  that 
followed  in  obtaining  blood  for  testing  for  the  Wassermann 
reaction.  It  may  be  stated  here  that  on  more  than  one 
occasion  the  needle  had  to  be  withdrawn  from  the  vein, 
regardless  of  the  fact  that  blood  was  flowing  freely.  It 
must  be  remembered  that  for  making  the  Wassermann 
test  it  is  not  necessary  for  the  point  of  the  needle  to 
be  entirely  in  the  vein  in  order  to  secure  enough  blood 
for  the  test,  whereas  in  introducing  a  fluid  like  salvarsan 
it  is  very  important  that  the  point  of  the  needle  should 
be  entirely  within  the  lumen  of  the  vein  and  nowhere 
else.  In  fact,  the  most  important  part  of  the  injection 
consists  in  the  proper  introduction  of  the  needle,  as  it 
may  be  partly  outside  of  the  vein,  or  may  go  too  deeply  or 
not  deeply  enough,  or  it  may  enter  between  the  layers  of 
the  vein  wall  or  between  the  vein  wall  and  the  perivenous 
tissues.  The  greatest  source  of  error  lies,  therefore,  in  the 
improper  manipulation  of  the  needle.  The  chances  for  mak- 
ing this  error  are  considerably  enhanced  by  the  use  of 


224      SEROLOGY    OF    NERVOUS   AND    MENTAL   DISEASES 

peculiar  needles  devised  especially  for  the  injection  of 
salvarsan — needles  that  have  a  peculiar  curve  with  a  flat 
piece  of  metal  attached  to  them,  of  which  the  Schreiber 
needle,  illustrated  in  Fig.  25,  is  the  prototype.  In  order 
to  manipulate  such  a  needle  the  physician  must  train  his 
fingers  to  grow  accustomed  to  handling  a  bent  instrument. 

No  better  needle  can  be  used  than  an  ordinary  straight 
one  with  a  stilet  to  prevent  rusting.  A  very  important 
point  in  the  introduction  of  the  needle  is  the  peace  of  mind 
of  the  operator,  a  desideratum  particularly  essential  in 
difficult  cases  with  poor  veins.  For  this  reason  alone  the 
author  believes  that  an  attachment  for  giving  the  salt 
solution  should  always  be  a  part  of  every  apparatus  used 
for  the  injection  of  salvarsan.  When  the  operator  knows 
that  salt  solution  will  be  used,— a  method  incapable  of  pro- 
ducing untoward  local  effects  even  when  the  perivenous 
tissues  are  infiltrated, — his  confidence  will  be  more  conducive 
to  the  proper  handling  of  the  needle  than  if  no  preliminary 
salt  injection  were  used.  For  this  reason,  therefore,  it  is  of  the 
greatest  advantage  that  the  apparatus  carry  a  container  of 
salt  solution  that  can  be  used  at  any  time  during  the  injection. 

To  return  to  the  introduction  of  the  needle :  Although  this 
procedure  was  fully  considered  under  the  head  of  Technology, 
this  did  not  include  the  method  for  introducing  drugs. 
For  this,  as  was  previously  emphasized,  a  special  technic  is 
required.  It  is  most  essential,  before  making  the  puncture, 
that  the  operator  be  absolutely  certain  that  the  vein  has 
the  proper  prominence,  is  well  fixed,  and  that  the  vein 
selected  is  the  most  suitable  one  the  patient  possesses.  It 
is  good  practice,  therefore,  to  spend  a  few  minutes  in  select- 
ing a  vein  and  judging  which  arm  is  best  suited  to  receive 
the  injection.  If  it  is  possible  to  use  the  left  arm,  this  should 
be  selected  by  right-handed  operators  in  preference  to  the 
right.  The  reason  for  taking  this  precaution  lies  in  the  fact 
that  the  largest  and  most  superficial  vein  at  the  bend  of  the 
elbow  runs  in  a  direction  from  right  to  left  and  upward, 
which  is  exactly  the  line  of  force  used  by  a  right-handed 
operator  in  puncturing  a  vein.  Where  the  veins  in  the  left 
arm  are  defective  and  the  right  arm  is  more  suitable,  it 


Fig.  27. — Appearance  of  scar  four  months  after  an  infiltration  of  the 
perivenous  tissues  with  salvarsan,  due  to  improper  introduction  of  the 
needle.  The  needle  had  to  be  removed  and  inserted  into  another  vein 
exposed  by  an  incision;  the  scar  can  be  seen  below. 


Fig.  28. — Intravenous  injection  of  salvarsan.  Note  the  three-way 
cock  near  the  operator's  hand,  also  the  two  rubber  bands  and  the 
carbon  filter  containing  sterile  normal  salt  solution,  fixed  to  the  side 
of  the  large  cylinder  with  one  of  the  rubber  bands. 


THE   TECHNIC   OF    INJECTION  225 

becomes  necessary  for  the  operator  so  to  place  himself  that 
the  same  direction  of  force  may  be  exerted  in  puncturing  the 
vein  as  was  just  described.  Use  every  means  to  render  the 
vein  prominent  (see  Technology);  grasp  the  arm  firmly, 
and  have  absolute  control  of  the  area  to  be  punctured. 

In  preparing  the  drug  the  author's  apparatus  possesses 
some  advantages  over  the  other  salt-carrying  three-way-cock 
outfits.  The  method  of  use  is  as  follows :  Pour  the  required 
amount  of  water  in  the  cylinder,  using  hot  water  for  salvarsan 
and  cold  for  neosalvarsan.  Having  properly  dissolved  the 
drug,  place  the  perforated  rubber  stopper  tightly  over  the  open- 
ing, securing  the  same  with  two  stout  rubber  bands;  in  order 
that  the  bands  may  not  slip  from  the  bottom  of  the  cylinder, 
it  is  best  to  attach  adhesive  plaster  to  the  rim  of  the  vessel. 
Place  a  sterile  towel  over  the  opening,  having  first  secured 
the  salt-carrying  carbon  filter;  turn  the  three-way  cock  so 
that  it  will  deliver  salt,  and  then  invert  the  entire  device. 
Hang  the  apparatus  on  a  hook,  place  some  salt  solution  in 
the  carbon  filter,  and  drive  out  all  air  from  the  rubber  tubing 
by  raising  and  lowering  the  glass  point  of  the  delivery  attach- 
ment. The  cock  should  now  be  turned  so  as  to  deliver  the 
drug,  and  the  air  expelled  from  the  rubber  tubing  leading  to 
the  delivery  cylinder.  Turn  the  cock  back  again  to  the 
salt  delivery  tubing,  and  the  apparatus  is  ready  for  use. 

Having  properly  cleansed  the  bend  of  the  elbow  and 
rendered  the  veins  as  prominent  as  possible,  with  four 
fingers  of  the  left  hand  of  the  operator  under  the  elbow  of  the 
patient  and  with  the  thumb  holding  the  vein  firmly  in  place 
and  in  close  contact  with  the  overlying  skin,  place  the  point 
of  the  needle  directly  in  front  of  the  thumb,  bevel  up,  and 
with  a  firm,  steady  thrust  push  the  point  into  the  vein.  As 
soon  as  a  sense  of  diminished  resistance  is  experienced  by  the 
right  hand  not  the  slightest  force  must  be  used  any  longer, 
and  the  needle  must  be  kept  in  exactly  the  same  place, 
without  the  slightest  deviation  from  the  original  position. 
When  the  blood  begins  to  flow,  collect  some  in  a  test-tube 
for  a  Wassermann  reaction.  Insert  the  delivery  point  into 
the  rubber  attachment  of  the  needle,  and  permit  about 
25  c.c.  of  the  salt  solution  to  flow  into  the  vein.     If  no 

15 


226      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

bulging  occurs,  the  needle  is  probably  in  the  right  place;  if 
the  slightest  swelling  occurs  about  the  vein,  the  needle  is  not 
properly  inserted,  despite  the  fact  that  the  blood  may  have 
flown  very  freely.  Once  infiltration  takes  place,  the  vein  is 
no  longer  fit  to  receive  the  salvarsan, — at  least  for  the 
present  injection, — and  another  vein  must  be  selected  for 
this  purpose.  The  physician  should  never,  under  any 
circumstances,  attempt  to  inject  salvarsan  where  bulging 
has  taken  place  with  salt  solution. 

It  occasionally  happens  that  the  needle  is  in  the  right 
position,  and  yet  the  salt  solution  does  not  seem  to  flow  into 
the  vein;  this  can  be  seen  through  the  glass  connection  piece 
of  the  delivery  point,  which  shows  a  trace  of  blood.  This  is 
sometimes  due  to  an  intravenous  pressure  that  is  greater  than 
the  pressure  in  the  delivery  apparatus;  if  the  apparatus  is 
elevated,  thus  increasing  the  pressure,  the  saline  solution 
will  begin  to  flow,  and  the  blood  from  the  connecting  tube 
will  disappear. 

Having  ascertained  to  his  satisfaction  that  the  point  of 
the  needle  is  in  the  vein,  as  shown  by  the  steady  flow  of 
the  saline  solution  and  the  absence  of  bulging,  the  phys- 
ician now  turns  the  cock  to  deliver  the  drug;  this  can 
be  accomplished  by  the  free  hand  of  the  operator,  taking 
care  not  to  change  the  position  of  the  needle  in  the 
slightest  degree.  The  turning  of  the  salvarsan  solution 
into  the  vein  causes  bubbles  of  salvarsan  to  rise  in  the 
air  vent  of  the  apparatus,  so  that  the  operator  has  at  all 
times  a  gage  as  to  the  rapidity  of  the  flow,  and  can  tell  at  a 
glance  whether  or  not  the  apparatus  is  functionating  prop- 
erly. The  introduction  of  a  full  dose  of  salvarsan  (0.6  gm.) 
should  take  about  fifteen  to  twenty  minutes;  for  the  ad- 
ministration of  neosalvarsan  less  time  is  required.  One 
should  not  attempt  to  increase  the  rate  of  flow  by  pushing 
in  or  withdrawing  the  needle,  as  such  manipulation  may 
interfere  with  the  success  of  the  injection,  either  in  whole 
or  in  part.  Occasionally  one  may  be  permitted  to  turn  the 
point  slightly  on  its  long  axis  so  as  to  change  the  relation  of 
the  bevel  to  the  vein  wall ;  this  must,  however,  be  done  with 
the  greatest  caution.    When  the  flow  is  interrupted,  a  fact 


ILL  EFFECTS   ACCOMPANYING   THE   INJECTION        227 

that  can  be  ascertained  by  the  cessation  of  the  bubbles 
rising  in  the  air-vent  tube,  it  is  well,  in  order  to  reestablish 
the  flow,  to  turn  on  the  salt  stream  before  attempting  to 
correct  or  improve  the  position  of  the  needle. 

The  apparatus  used  by  the  author  is  very  simple  and 
permits  of  mixing  in  the  same  container  that  delivers  the 
liquid;  the  water  necessary  for  the  solution  of  the  drug  can 
be  carried  in  the  same  cylinder,  and  the  rate  of  flow  or  its 
cessation  can  be  ascertained  at  a  glance.  This  last  is  a  very 
important  feature,  and  one  that  the  other  apparatus  do  not 
possess.  Another  advantage  not  possessed  by  other  ap- 
pliances is  the  ability  to  inject  a  pure  solution  of  salvarsan 
without  the  least  admixture  of  bits  of  glass  or  other  insoluble 
debris  that  are  at  times  present  in  a  solution  of  salvarsan. 
No  matter  how  careful  the  preparation  of  the  drug,  one  will 
only  in  rare  cases  obtain  an  absolutely  clear  solution,  and  the 
delivery  glass  tube  projecting  slightly  above  the  rubber 
stopper  permits  the  impurities  to  settle  on  top  of  it,  and  these 
are  not  injected  into  the  vein. 

After  the  requisite  amount  of  remedy  has  been  injected, 
the  saline  solution  is  again  permitted  to  flow  into  the  vein, 
so  that  at  no  time  does  the  salvarsan  come  in  contact  with 
the  perivenous  tissues,  and  after  a  few  cubic  centimeters 
have  been  introduced  the  needle  is  quickly  withdrawn 
and  the  site  of  puncture  bandaged.  The  aseptic  precautions 
are  the  same  as  those  observed  in  performing  hypodermo- 
clysis. 

ILL  EFFECTS  ACCOMPANYING  THE  INJECTION 

In  the  vast  majority  of  instances  the  entire  procedure 
is  attended  by  very  little  discomfort.  Extremely  nervous 
patients  may  complain  of  faintness  and  require  smelling 
salts.  Only  rarely  will  a  patient  complain  of  pain  in  the 
arm-pit  corresponding  to  the  site  of  injection.  At  times  the 
continuous  flow  of  salvarsan  against  a  slightly  injured  wall 
on  the  opposite  side  of  the  vein  will  cause  a  smarting  pain 
at  the  point  of  injection.  This,  as  well  as  the  pain  in  the 
axilla,  can  be  readily  overcome  by  stopping  the  flow  of 
salvarsan  and  turning  on  the  saline  solution.    Saline,  there- 


228      SEROLOGY   OF   NERVOUS    AND   MENTAL   DISEASES 

fore,  plays  a  threefold  role — it  relieves  the  anxiety  of  the 
operator,  it  gives  him  a  simple  aid  in  ascertaining  the  ac- 
curacy of  the  needle's  position  without  injuring  the  patient, 
and  when,  in  the  course  of  injection,  accidents  such  as  those 
mentioned  do  occur,  he  can  always  use  the  salt  solution  with 
impunity. 

Studies  on  the  variation  in  the  blood-pressure  were  con- 
ducted by  Sieskind  from  the  service  of  Wechselmann,  and 
showed  that,  in  the  majority  of  instances,  the  blood-pressure 
is  lowered.  This  is  in  accord  with  the  observations  of  Nicolai, 
who  finds  a  lowering  of  the  blood-pressure  after  the  subcu- 
taneous injection  of  arsenical  preparations.  This  lowering 
is  not  very  marked,  and  is  not  sufficient  to  justify  the  ex- 
clusion of  salvarsan. 

Some  patients  experience  an  increased  flow  of  saliva  during 
salvarsan  administration;  this  disappears,  however,  in  less 
than  an  hour. 

AFTER-CARE  OF  THE  PATIENT 

After  receiving  the  injection  it  is  best  for  the  patient  to 
remain  in  bed.  It  may,  at  times,  be  permissible  to  give 
the  injection  in  the  physician's  office,  provided  the  patient 
is  robust  and  does  not  present  active  manifestations  of  the 
disease,  such  as  crises  or  lancinating  pains.  The  author  has 
had  no  difficulty  in  sending  patients  to  their  homes,  even 
when  they  had  to  travel  an  hour  or  more.  In  selected  cases 
this  may  be  done  with  impunity,  provided  the  full  strength 
of  the  drug  was  not  injected  and  when  neosalvarsan  was 
used.  With  full  doses,  and  with  salvarsan,  it  is  better  to 
give  the  injection  at  the  patient's  home.  It  is  quite  unneces- 
sary to  send  the  patient  to  a  hospital  to  receive  the  injec- 
tion. 

In  order  to  avoid  the  intestinal  irritation  which  some 
patients  seem  to  develop  a  small  dose  of  Epsom  salts  may  be 
administered,  which  will  remove  the  irritating  drug  as  it  is 
eliminated  from  the  system.  This  is  particularly  indicated 
in  those  cases  where  habitual  constipation  exists. 

When  the  injection  is  given  at  bedtime,  no  dietetic  orders 
need  be  given;  where,  however,  the  treatment  is  given  during 


INDICATIONS   AND   CONTRAINDICATIONS  229 

the  day,  it  is  best  to  direct  that  solid  food  should  be  omitted 
until  the  following  day.  A  small  portion  of  soup  or  a  cup  of 
weak  tea  may  be  permitted  a  few  hours  after  the  treatment. 
Some  patients  are  by  nature  very  restless,  and  for  these  a 
small  dose  of  a  mild  sedative  will  do  no  harm.  The  ordinary 
case  needs  no  special  attention,  particularly  when  neo- 
salvarsan  is  administered.  The  morning  following  the  in- 
jection an  analysis  of  the  urine  must  be  made,  a  precaution 
that  should  also  be  observed  before  making  the  injection. 

Where  facilities  for  performing  the  Wassermann  reaction 
are  at  hand,  as  is  the  case  in  the  majority  of  hospitals  and 
in  medical  centers,  the  specimen  of  blood  obtained  during 
the  introduction  of  the  needle  should  not  be  discarded,  but 
be  utilized  for  making  an  analysis.  The  greater  the  number 
of  Wassermann  tests  performed  on  a  patient,  the  greater  the 
good  that  will  redound  to  the  patient  and  to  the  physician. 
It  is  impossible  at  present  to  treat  a  case  of  syphilis  intelli- 
gently without  making  a  number  of  Wassermann  tests. 
This  will  be  discussed  more  fully  under  the  head  of  In- 
dications and  Contraindications. 

The  treatment  of  a  patient  who  shows  pathologic  mani- 
festations after  receiving  the  injection  will  be  given  in  the 
section  on  Post-salvarsan  Manifestations. 

INDICATIONS  AND  CONTRAINDICATIONS 

Indications. — In  this  connection  only  neurologic  cases 
will  be  considered.  The  clinical  and  serologic  symptoms 
requiring  treatment  will  be  considered  together.  It  is  fairly 
well  established  that  the  syphilogenous  diseases  of  the  nervous 
system  all  demand  specific  treatment,  and  the  active  varieties 
of  these  diseases  require  more  attention  than  do  the  more  or 
less  quiescent  types.  Preeminently  among  the  former  is 
cerebrospinal  syphilis. 

In  cerebrospinal  lues,  particularly  with  an  abundant 
pleocytosis,  the  therapy  must  be  correspondingly  active,  and 
this  regardless  of  the  behavior  of  the  Wassermann  reaction, 
as  but  little  in  the  way  of  therapy  need  be  given  to  overcome 
this  index  of  existing  syphilis. 


230      SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

The  next  to  be  considered  is  tabes.  The  serology  of  this 
disease  is  varied,  and  phenomena  are  seen  that  resemble 
cerebrospinal  lues  on  the  one  hand  and  general  paresis  on 
the  other.  Again,  there  are  instances  in  which  biologic  tests 
give  no  clue  as  to  the  existence  of  neurologic  syphilis. 

In  this  disease  one  must  be  satisfied  with  removing  sub- 
jective sensations,  as  the  objective  pupillary  and  reflex 
abnormalities  cannot  be  regarded  as  removable  by  therapy. 
Here  serologic  analyses  are  of  the  greatest  moment,  both 
as  an  index  to  treatment  and  from  a  prognostic  standpoint. 
The  higher  the  cell  count  in  the  spinal  fluid  in  a  given  case 
of  tabes,  the  greater  the  benefit  that  will  be  derived  from 
antiluetic  medication,  and  the  quicker  the  result  obtained. 
This  was  pointed  out  in  the  description  of  Hyper- 
lymphocytic  Tabes,  which  is,  from  a  prognostic  viewpoint, 
the  most  satisfactory  type  of  tabes  to  treat. 

Where  the  Wassermann  reaction  persists,  treatment  can- 
not be  said  to  be  concluded,  and  such  "Wassermann  fast" 
tabetics  are  best  kept  under  surveillance  until  the  reaction 
becomes  negative,  or,  in  other  words,  indefinitely.  It  is 
remarkable  that  where  the  "Wassermann  fast"  phenomenon 
is  obtained,  the  patients,  as  a  rule,  can  tolerate  enormous 
quantities  of  salvarsan,  administered  at  regular  intervals, 
from  20  to  30  injections  being  readily  borne. 

The  question  of  treating  a  tabetic  that  evinces  no  active 
serologic  signs  depends  entirely  upon  the  clinician's  judg- 
ment and  upon  the  subjective  manifestations  of  the  given 
case.  Where  marked  discomfort,  is  experienced  from  crises 
and  shooting  pains,  the  remedy  may  be  employed  and  in 
some  instances  will  be  of  benefit.  The  patient  who  presents 
the  serologic  and  clinical  combination  under  consideration 
most  likely  suffers  from  a  pathologic  change  of  an  exudative 
nature,  that  runs  its  course  entirely  within  the  intervertebral 
foramen,  as  is  suggested  in  Part  III  of  this  volume. 

Whether  or  not  a  patient  with  general  paresis  should  be 
treated  specifically  is  as  yet  an  open  question.  In  view  of  the 
fact  that  but  little  is  known  regarding  the  effects  that  may 
be  secured  from  salvarsan  and  neosalvarsan,  it  is  justifiable 
to  try  out  this  form  of  treatment  on  such  patients.     As 


INDICATIONS    AND    CONTRAINDICATIONS  231 

will  be  shown  further  on,  some  improvement,  clinically  at 
least,  is  occasionally  attained. 

The  same  serologic  consideration  is  to  be  given  the  selec- 
tion of  cases  for  therapy  as  applies  to  other  syphilitic  dis- 
eases of  the  nervous  system,  i.  e.,  the  greater  the  cell  count- 
say,  over  60  or  70  per  c.mm. ,— the  more  will  the  given 
patient  be  benefited.  If  the  serology  shows  the  combina- 
tion of  findings  suggestive  of  the  early  stage  of  the  disease, 
when  comparatively  little  deterioration  has  taken  place, 
this  would  point  to  the  use  of  specific  medication.  In  general 
it  may  be  said  that  less  hope  can  be  offered  to  the  case  with  a 
persistent  positive  Wassermann  with  a  low  cell  count  than 
to  the  patient  who  shows  the  early  serology,  or  a  high  cell 
count,  or  whose  Wassermann  becomes  negative  after  receiv- 
ing a  series  of  intravenous  injections.  It  is  a  well-known  fact 
that  in  rare  cases  the  absent  knee-jerks  have  returned  and  in 
general  paresis  the  defective  memory  and  the  speech  dis- 
turbance disappeared.  The  greatest  caution  must  be  ob- 
served in  stating  positively  that  this  or  that  case  is  beyond 
improvement,  the  better  plan  being  to  experiment  with  the 
different  methods  and  with  the  new  remedies,  either  alone 
or  in  combination  with  mercury;  of  this,  more  will  be  ad- 
duced later. 

Having  once  secured  complete  negativation  of  the  sero- 
logic picture,  the  patient  should  be  advised  to  return  once 
every  two  or  three  months  to  ascertain  if  there  is  a  recur- 
rence. A  return  of  pathologic  findings  is  an  index  to  further 
therapy. 

Contraindications. — If  one  considers  the  fact  that  during 
the  comparatively  short  time  that  has  elapsed  since  the 
original  publication  of  Alt  (in  March,  1911),— a  period  of 
three  years,— over  5,000,000  doses  of  salvarsan  and  neosal- 
varsan  have  been  used,  it  is  small  wonder  that  one  still 
bears  in  mind  the  untoward  effects  produced  by  the  remedy. 
The  ill  effects  obtained  and  published  in  three  years  naturally 
present  a  formidable  array  of  danger-signals,  which  are 
responsible  for  much  hesitation  in  the  use  of  the  drug. 
If  the  physician  will  pause  to  consider  the  fact  that  millions 
of  doses  of  this  remedy  have  been  used,  he  will  see  that  the 


232      SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

element  of  danger  in  the  use  of  salvarsan  is  no  greater  than 
in  the  use  of  mercury,  quinin,  or  morphin.  If  the  number  of 
accidents  per  thousand  administrations  of  the  last-named 
remedies  were  calculated,  the  proportion  would  be  no 
greater  than  follows  the  use  of  salvarsan  or  neosalvarsan. 
In  a  comparatively  short  time  after  its  introduction  accidents 
were  reported  from  the  use  of  the  drug,  but  it  was  later  shown 
that  the  method  of  administration  (depot  formation,  use  of 
impure  water,  improper  selection  of  patients,  etc.)  was  more 
to  blame  than  the  toxicity  inherent  in  the  drug.  Our  knowl- 
edge of  the  use  of  salvarsan  having  increased,  the  complica- 
tions following  its  injection  are  becoming  fewer  and  fewer, 
so  that  the  contraindications  pointed  out  by  some  writers 
are  being  regarded  somewhat  lightly,  and  only  the  indication 
is  regarded  as  governing  its  use.  In  the  author's  experience 
the  drug  has  proved  a  harmless  one — much  more  so  than  the 
extensive  literature  on  the  subject  would  indicate.  The 
contraindications  to  its  introduction  must  be  few,  and, 
moreover,  these  must  be  generally  recognized. 

The  weeding  out  of  cases  for  salvarsan  therapy  may  be 
divided  into  two  classes:  (1)  Those  to  whom  salvarsan  is  to 
be  given  with  great  caution  only,  and  (2)  those  to  whom 
salvarsan  cannot  be  administered  at  all.  To  class  1,  properly 
speaking,  belong  those  patients  who  are  to  receive  the  drug, 
but  who  will  require  close  watching;  these  cases  are  the  early 
forms  of  cerebral  lues  with  cranial  nerve  manifestations  of  an 
exudative  nature — cases  that  usually  come  first  to  the  oph- 
thalmologist or  aurist.  In  these  cases,  even  if  a  small  dose 
is  injected,  we  may  in  a  short  time  have  to  deal  with  a  cere- 
bral Herxheimer  reaction  (see  Post-salvarsan  Manifesta- 
tions), which,  considering  the  importance  of  the  locality, 
in  the  case  of  the  eighth  nerve,  the  pons  and  medulla,  would 
demand  that  extreme  caution  be  exercised  in  advising  the 
injections,  more  so  since  we  know  that  one  injection  is  as 
efficient  in  a  case  of  cerebral  lues  as  is  a  single  injection  of 
mercury  salicylate.  One  injection,  therefore,  will  tend  only 
to  increase  the  number  of  failures  in  this  use  of  salvarsan, 
and  be  prejudicial  to  the  treatment.  Many  of  the  so-called 
dangers  are,  in  reality,  due  to  the  mode  of  administration, 


INDICATIONS   AND   CONTRAINDICATIONS  233 

which  the  statistics  of  1913  seem  to  corroborate  from  the 
fact  that  since  the  necessary  precautions  were  more  care- 
fully observed,  and  since  the  administration  of  salvarsan  was 
generally  performed  with  greater  skill,  fewer  casualties  took 
place.  With  these  points  in  mind,  the  real  danger  of  ad- 
ministering salvarsan  and  the  contraindications  from  a 
clinical  point  of  view  are  few  indeed.  It  frequently  be- 
comes necessary  to  treat  patients  with  a  high  blood-pressure 
with  salvarsan.  The  author  treated  one  patient  with  a 
blood-pressure  of  240,  and  obtained  no  ill  effects  beyond 
nausea  and  vomiting.  The  organs  of  excretion  were  nor- 
mal. Where  the  blood-pressure  is  much  below  normal,  the 
use  of  salvarsan  is  dangerous,  its  injection  being  followed 
by  a  temporary  lowering  of  the  pressure.  Such  patients 
must  be  observed  carefully,  and  if  the  pressure  becomes 
low  enough  to  cause  symptoms  of  distress,  an  injection  of 
a  few  minims  of  adrenalin  chlorid  may  be  used  with  ad- 
vantage. 

In  neurologic  practice  one  is  not  infrequently  called  upon 
to  treat  tabes  with  beginning  optic  atrophy.  These  patients, 
even  if  they  do  display  active  clinical  and  serologic  mani- 
festations, should  receive  salvarsan  or  neosalvarsan  with  the 
greatest  caution.  It  is  advisable  to  administer  at  first  a 
very  small  dose  of  neosalvarsan  and  carefully  observe  its 
effect  on  the  optic  nerve,  both  subjectively  and  objectively. 
Any  change  for  the  worse,  be  it  ever  so  mild,  precludes  the 
further  use  of  the  drug.  It  must  be  remembered  that  the 
amaurosis  resulting  from  salvarsan  or  from  neosalvarsan  is 
very  refractory  to  treatment. 

Of  the  contraindications  to  the  use  of  salvarsan  should  be 
mentioned :  Severe  uncompensated  heart  disease — where  on 
the  slightest  exertion,  and  even  while  resting,  there  is  more 
or  less  dyspnea,  particularly  when  the  pulse  shows  irregu- 
larities. Coronary  sclerosis,  particularly  when  accompa- 
nied by  a  urine  of  low  specific  gravity  (contracted  kidney), 
and  containing  albumin  and  casts.  Emphysema  and  chronic 
bronchial  affections  that  affect  the  heart  should  be  treated 
with  the  greatest  caution,  and  with  small  doses  only.  Even 
if  syphilis  is  present  in  a  patient  with  advanced  diabetes, 


234      SEROLOGY   OF   NERVOUS   AND   MENTAL  DISEASES 

carcinoma,  or  tuberculosis,  salvarsan  should  not  be  given, 
as  miracles  cannot  be  expected  to  follow  its  use. 

Aortic  aneurysm  in  the  very  advanced  stage  will  not  be 
benefited  by  salvarsan,  and  its  administration  may  be  the 
direct  cause  of  the  patient's  demise.  This  contraindication 
is  removed  when  the  condition  is  less  advanced  and  when  the 
remainder  of  the  cardiac  apparatus  is  intact.  If  the  luetic 
focus  is  near  an  important  and  vital  center,  such  as  the 
vagus  or  other  important  medullary  centers,  the  use  of  sal- 
varsan is  very  dangerous  on  account  of  the  possible  produc- 
tion of  a  Herxheimer  reaction  in  this  region,  causing  almost 
certain  death.  This  will  be  considered  more  fully  together 
with  the  Herxheimer  reaction. 

Where  an  early  cerebral  lues  manifests  itself  by  headache, 
vertigo,  defective  memory,  apoplectic  seizures  that  leave  per- 
manent paralyses  in  their  wake,  salvarsan  should  be  given 
with  great  caution,  as  its  use  may  result  in  added  insult  to 

the  brain. 

THE  WATER  ERROR 

The  early  literature  on  salvarsan  and  its  by-effects  con- 
tains many  references  to,  and  examples  of,  the  toxic  effects 
of  the  drug,  This  resulted  in  extensive  experimentation  to 
ascertain  the  cause  of  the  toxicity,  and  it  was  subsequently 
shown  that  the  trouble  was  not  inherent  in  the  salvarsan, 
but  in  the  water  used  in  making  the  solution.  Mcintosh 
and  Fildes  and  Dearden,  from  the  laboratory  of  William 
Bulloch,  working  with  various  ordinary  and  bacterium-free 
saline  injections  in  rabbits,  came  to  the  conclusion  that  it 
was  not  the  salvarsan,  but  the  bacteria  contained  in  the 
media  used  to  effect  its  solution,  that  should  be  held  re- 
sponsible for  the  ill-effects  of  the  drug. 

As  a  result  of  the  suggestions  of  Ehrlich  and  Wechselmann, 
Yakimoff  and  N.  K.  Yakimoff  learned  the  effects  upon 
animals  of  the  injection  of  solutions  containing  the  toxins 
and  endotoxins  of  bacteria.  These  investigators  found 
that  the  injection  of  small  doses  of  salvarsan  together  with 
the  endotoxin  of  Bacterium  coli  commune  in  mice  infected 
with  trypanosomes  proved  much  more  toxic  than  did  endo- 
toxin-free  injections.    These  writers  established  the  toxicity 


THE   FATE   OF   THE    DRUG   IN   THE    ORGANISM         235 

for  the  endotoxins  of  Bacterium  coli  commune,  for  the 
Bacillus  pyocyaneus,  Staphylococcus  aureus,  Pneumobacil- 
lus  Friedlanderi,  Bacillus  subtilis,  and  Bacillus  tetragenus. 

The  addition  of  these  endotoxins  to  salvarsan  injected 
intravenously  will  result  in  a  toxic  effect,  multiplying  this 
toxicity  for  mice  from  two  to  eight  times.  The  same  amount 
of  endotoxin  injected  without  the  addition  of  salvarsan  is 
without  bad  effect  on  the  animals.  The  increase  of  toxicity 
produced  by  different  bacteria  also  varies,  the  endotoxin  of 
Bacterium  coli  being  the  most  dangerous  of  all,  and  that  of 
Bacillus  tetragenus  least  toxic.  The  reason  for  using  freshly 
distilled  water  is  apparent  from  the  foregoing  report,  and 
the  precaution  of  always  using  this  should  be  strictly  fol- 
lowed. The  simple  boiling  of  old  distilled  water  may  result 
in  the  injection  of  sufficient  endotoxin  together  with  the 
salvarsan  to  produce  all  the  untoward  effects  unjustly  as- 
cribed to  the  drug. 

THE  FATE  OF  THE  DRUG  IN  THE  ORGANISM 

The  presence  of  the  injected  drug  is  demonstrable  at  once 
in  the  blood  drawn  from  the  other  arm;  it  may  also  be 
demonstrated  in  the  urine  voided  during  the  operation  or 
immediately  following  it.  Sufficient  data  are  recorded  to 
show  that  the  excretion  of  arsenic  begins  at  once,  and  con- 
tinues for  a  long  time.  The  duration  of  this  period  of  ex- 
cretion depends  greatly  upon  the  condition  of  the  excretory 
organs  of  the  patient,  and  upon  the  method  of  introducing 
the  drug;  it  remains  in  the  body  much  longer  after  an 
intramuscular  than  after  an  intravenous  injection.  In 
from  three  to  four  days  the  arsenic  can  no  longer  be  found 
in  the  urine,  but  it  may  still  be  present  in  the  feces  after 
five  or  six  days.  Some  writers  have  found  arsenic  even 
after  four  weeks,  and  Finger  reports  its  presence  nine  months 
after  a  single  salvarsan  injection.  The  elimination  of  the 
drug  is  so  rapid  that  it  is  imperative  to  use  repeated  doses 
before  an  effect  can  be  observed. 

The  ordinary  tests  for  the  presence  of  arsenic  in  the 
cerebrospinal  fluid  after  an  injection  of  salvarsan  gave,  as 
a   rule,   negative  results.     The  reports  of  Wechselmann, 


236     SEROLOGY    OF    NERVOUS    AND    MENTAL    DISEASES 

Sicard  and  Bloch,  and  Zaloziecki,  using  the  Marsch-Bertrand 
apparatus,  as  well  as  the  biologic  method  of  Abel  (see  be- 
low), showed  that  arsenic  is  present  in  the  spinal  fluid  of 
patients  treated  with  salvarsan.  This  is  to  be  expected, 
and  to  say  that  the  drug  does  not  reach  the  spinal  fluid, 
in  view  of  the  fact  that  the  serology  is  markedly  changed 
in  every  way,  is  to  establish  an  unexplainable  paradox. 
The  presence  of  arsenic  in  the  fluid  puts  all  controversy  as  to 
the  modus  operandi  of  the  negativating  forces  to  an  end: 
it  simply  attacks  the  microorganisms  in  situ. 

By  using  the  biologic  method  for  detecting  arsenic,  the 
author  was  able  to  demonstrate  its  presence  in  the  vomitus 
of  a  patient  treated  with  salvarsan. 

THE  DETECTION  OF  ARSENIC 

The  chemical  detection  of  arsenic  will  be  described  after 
the  biologic  detection  has  been  considered;  the  biologic 
method  was  employed  by  the  author  in  his  studies  of  arsenic 
elimination. 

This  method  is  dependent  upon  the  growth  and  prolif- 
eration of  a  thread-like  fungus,  which,  when  brought  in 
contact  with  a  substance  containing  arsenic,  gives  off  a 
strong,  garlic-like  odor.  The  reaction  is,  therefore,  only 
qualitative,  as  the  sense  of  smell  of  the  individual  worker 
must  be  considered.  The  chemistry  of  the  reaction  depends 
upon  the  formation,  in  part,  of  hydrogen  arsenid,  AsH3,  and 
largely  on  the  production  of  diethylarsin,  AsH(C2H5)2, 
when  the  fungus  is  brought  in  contact  with  an  arsenic- 
containing  substance.  The  presence  of  the  chemical  sub- 
stances just  mentioned  is  responsible  for  the  garlic-like  odor. 

The  fungus,  Penicillium  brevicaule,  grows  very  readily 
upon  doubly  sterilized  potato,  as  well  as  upon  white  or 
brown  bread.  The  growth  is  very  persistent,  and  a  dried-up 
potato  culture  eight  months  old  will  still  give,  upon  recul- 
ture,  a  vigorous  growth  of  fungi.  The  fungi  grow  at  room 
temperature  or  at  32°  C.  in  the  incubator.  In  the  course 
of  time  the  growth  becomes  yellowish  and  then  brown,  a 
fact  that  does  not  interfere  with  the  arsenic-detecting 
properties. 


Fig.  29. — Penicillium  brevicaule.     (No.  6  Leitz,  ocular  4.) 


THE  DETECTION  OF  ARSENIC  237 

The  technic  is  very  simple,  and  does  not  consume  more 
than  five  minutes  of  the  worker's  time.  Having  obtained 
the  spinal  fluid  in  the  ordinary  way,  it  is  poured  upon  a  cul- 
ture previously  grown  on  white  bread  (preferably  two  days 
old)  in  an  Erlenmeyer  flask,  and  stoppered  tightly  with  a 
rubber  stopper.  It  is  permitted  to  remain  thus  tightly 
stoppered  for  forty-eight  hours  before  the  stopper  should 
be  removed  for  the  detection  of  the  garlic-like  odor.  Re- 
peated opening  of  the  flask  tends  to  diminish  the  intensity 
of  the  odor.  The  delicacy  of  the  test  surpasses  that  of  the 
ordinary  Marsh  test,  as  it  is  capable  of  giving  the  odor  of 
garlic  when  3-^0  milligram  of  salvarsan  is  brought  in  contact 
with  it,  and  as  salvarsan  contains  only  a  trifle  over  31  per 
cent,  of  arsenic,  the  test  is,  therefore,  sensitive  to  tuVo 
milligram  of  arsenic.  The  author  was  unable  to  detect 
the  odor  in  fluids  from  patients  treated  with  one  dose, 
but  when  frequently  repeated  doses  of  salvarsan  or  neo- 
salvarsan  were  given,  the  odor  could  be  obtained  in  from 
forty-eight  to  sixty  hours.  The  test  was  performed  in  the  fol- 
lowing manner:  The  bread-containing  Erlenmeyer  flasks 
were  sterilized  twice  and  carefully  inoculated  with  the 
Penicillium  brevicaule  fungus.  At  the  end  of  the  second  day 
of  growth  these  flasks  were  ready  for  use.  Having  obtained 
the  spinal  fluid,  10  c.c.  was  placed  in  the  flask  and  stoppered 
with  a  rubber  stopper.  The  cases  that  had  received  the  fore- 
going method  of  treatment  usually  showed  the  reaction,  pro- 
vided not  less  than  8  c.c.  of  the  fluid  was  used  in  making  the 
test.  After  making  three  intravenous  injections  no  trace 
of  the  drug  could  be  demonstrated  in  the  fluid,  but  after  the 
fourth  or  fifth  treatment  the  odor  could  readily  be  obtained. 
The  incubation  was  carried  out  on  top  of  the  incubator,  at  a 
temperature  varying  between  27°  and  30°  C.  In  performing 
this  experiment  care  must  be  taken  not  to  introduce  air 
bacteria  while  transferring  the  potato  culture  to  the  Erlen- 
meyer flask. 

The  Marsh  Test. — Nascent  hydrogen  converts  arsenic 
compounds  into  gaseous  hydrogen  arsenid,  AsH3.  This  can 
be  decomposed  by  heat,  the  arsenic  being  deposited  as  a  dark, 
mirror-like  coating  on  cold  objects.    This  is  practically  the 


238      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

basis  of  the  Marsh  test.  Where  minute  quantities  of  arsenic 
are  to  be  sought  for,  it  is  necessary  to  have  at  least  a  liter 
flask,  and  a  larger  amount  of  zinc  is  required  than  where  the 
search  is  for  larger  quantities  of  arsenic. 

To  begin  with,  all  reagents  must  be  arsenic  free.  The  liter 
flask  is  provided  with  a  separatory  funnel  that  reaches  to 
the  bottom  of  the  flask.  As  the  liberated  gas  will  contain 
moisture,  it  is  best  to  pass  this  through  a  U  -tube,  which  is 
immersed  in  cold  water,  and  through  another  tube  contain- 
ing dried  calcium  chlorid.  The  moisture  that  is  not  condensed 
in  the  first  U  tube  is  absorbed  in  the  calcium  tube.  The  dry 
gas  now  passes  through  a  horizontal  glass  tube  of  hard 


Fig.  30. — Apparatus  for  the  detection  of  a  minute  amount  of  arsenic 
by  Marsh's  test  (Rockwood). 


Bohemian  glass,  which  melts  with  great  difficulty.  After  all 
the  air  has  been  driven  off  from  the  apparatus,  this  tube 
should  be  heated  to  redness  with  a  Bunsen  burner,  and  the 
heating  continued  for  half  an  hour,  in  order  to  prove  the 
purity  of  the  reagents  used;  when  satisfactory,  the  apparatus 
is  ready  to  receive  the  material  to  be  tested  for  the  presence 
of  arsenic.  If  the  reagents  are  not  pure,  a  brown  or  black 
mirror  will  immediately  be  deposited  beyond  the  flame. 
The  mirror  of  arsenic  is  rendered  more  apparent  if  the  glass 
tube  beyond  the  flame  is  constricted  to  a  small  diameter, 
which  is  also  the  case  with  the  free  point  of  the  tube.  If  the 
arsenic  is  not  decomposed  at  the  constriction,  which  is  often 
the  case,  it  can  be  detected  by  the  flame  at  the  point  of  the 


INTRAVENOUS   AND   INTRASPINOUS   TREATMENT       239 

tube  with  a  cold  porcelain  surface,  upon  which  the  mirror 
collects. 

In  order  to  remove  the  exhausted  acid  without  the  ad- 
mission of  air  it  is  advisable  to  have  a  third  glass  tube  in- 
serted through  the  rubber  stopper,  with  a  bent  end  to  which 
a  rubber  tube  possessing  a  clamp  is  attached.  This  removal 
can  be  effected  by  opening  the  clamp  and  closing  the  exit 
tube  for  a  second,  when  the  fluid  siphons  off.  Where  very 
minute  amounts  of  arsenic  are  present,  it  may  be  necessary 
to  manipulate  the  apparatus  for  several  hours.  The  test 
is  sensitive  to  yro"  milligram  of  arsenic.  The  reaction  is  in- 
terfered with  or  prevented  by  the  presence  of  oxidizing  agents, 
organic  matter,  and  the  salts  of  the  heavy  metals,  particularly 
of  mercury. 

The  nascent  hydrogen  gas  is  generated  by  the  action  of 
chemically  pure  H2S04  upon  arsenic-free,  finely  granulated 
metallic  zinc. 

Other  tests  requiring  the  use  of  electric  apparatus  have 
also  been  devised;  these  will  not  be  described  here,  the 
reader  being  referred  to  special  works  on  analytic  chemistry 
for  a  discussion  of  them,  as  well  as  for  the  corroborative 
tests  for  the  detection  of  arsenic. 

THE  COMBINED  INTRAVENOUS  AND  INTRASPINOUS 
TREATMENT 

In  an  article  which  appeared  in  the  British  Medical  Jour- 
nal, November  15,  1913,  F.  W.  Mott  speaks  of  treating 
syphilis  of  the  nervous  system  by  a  method  conceived  by 
Fisher,  who  in  the  spring  of  1912  elaborated  it  in  the 
Rockwood  Hospital  in  Kingston,  Canada.  Fisher  at  that 
time  administered  to  his  patients  salvarsan  intravenously, 
and  after  having  succeeded  in  rendering  their  sera  negative 
to  the  Wassermann  test,  would  inject  this  serum  intra- 
spinously  every  week  for  three  months;  after  this  the 
patient  would  receive  the  same  treatment  every  two  weeks 
for  four  months.  Mott  observed  very  gratifying  results 
from  this  method  of  treatment,  so  that  he  had  Fisher 
come  to  London  to  continue  his  studies  on  patients  in  the 
Claybury  Hospital. 


t-    - 

+ 

+ 

+  -H      ++ 

+ 

■H  + 

++ 

■H 

+ 

8  I++I 

+ 

++I  ++ 

+ 

++ 

I++ 

+  1 

+ 

1 

©  _^ 

"3 
C 

§  2 

Q  O  ©  ©_  O 

<N- 

•*  o  o  o  o 

•f 

P® 

C  XCM 

©q 

© 

M 

<  * 

„_  © 

'&d 

rt^rtrt 

d 

Ortrt^d 

d 

-H''J 

r^da 

•H'*"5 

© 

■^ 

°'3 

•nonoeay; 

++J' 

+ 

+++++ 

+ 

+  ^ 

+  1  + 

+  ■« 

+ 

+ 

-H 

°£ 

6 

•nnn-Q  jaj 

CSJ.  t>  «-l  l> 

■* 

OOiN-*'* 

o 

coco 

COCMKl 

CMO 

■<*l 

CM 

gj 

sIIaO 

rH        r-: 

** 

HHrtrtH 

™* 

03^ 

•gnenxiassBM 
•niruag 

■H   1  -H  + 

+ 

++,++ 
++'++ 

-« 

X' 

'+t 

J' 

+ 
+ 

1 

.  :          -8SOQ 

~xxx© 

0 

XGC-tf  NO 

o 

oo 

■*C  X 

-*  *-< 

© 

1> 

5  g  =  2         IB^Oi 

a  p  o  ~ 

°,  TT  ■*  -#  5D 

o 

[0 

«TfON3 

oc; 

0O«tH 

Sl> 

-I 

O 

- 

mt§'S."3  -snotjoattq 

■*-*-*U5 

lO 

■*  ■*  o  -o  1C 

>o 

0000 

t>oo 

COO 

0 

e» 

53 

21  *-*    jo  aaqran  k; 

rt 

>* 

d            -asoQ 

a  -  -3  • 

■    -co    -    ■ 

j>oq 

qcirt 

C5©# 

l> 

X 

F-i 

Eh 

o  S 
►5  5 

I^oj, 

O    '    "='    ' 

■■'-'"■ 

co  cm' 

idcoid 

doo 

d 

^i 

<! 

Ph 

"S 

Zj>     i  •snonoatnj 

!      -r-l      - 

.     .00     -     • 

UJ^J( 

I>Ot> 

©>-H 

OS 

CM 

g 

O 

© 

~     j  jo  jaqrahx 

a 

•asorj 

d  O  00  o  >o 

CO 

■*  C |  K  ~.  30 

■* 

o  o 

u>io© 

©    . 

lO 

» 

§ 

IB^OX 

r£  C<i  CM  CM  CM* 

ci 

c4  ci  i-<  C4  CJ 

(N 

c4<n" 

i-HCMCO 

CO     ■ 

CO 

■* 

Q 

=3 

j>       i  -Bnonoafni 

tJOtIUS 

o 

W^tJOO 

lO 

uz  ■* 

coi-'io 

o    . 

l> 

■* 

<g         jo  ja'qrahx 

i— i 

•jnara^-eaij, 

a 

J° 

"gr-lCMCMCM 

csi 

NNMNN 

CO 

■*■* 

■*rjiia 

OM 

X 

W 

o 
u 

nOI^BJTlQ 

o 

o 

. 

.+++ 

- 

+++++ 

-i- 

++ 

+++ 

+ 

+ 

+ 

-3                          SO 

!+++« 

+ 

+++++ 

+ 

++ 

+++ 

++ 

+ 

+ 

g-g 

c3 

=5  S 

£JX©Tf  © 

CO 

■*  CO  •*  •*  N 

l-l 

o-* 

CDCMtH 

CMO 

*H 

© 

jj  5 

oh 
.2  o 

dJH 

oooh 

d 

dddod 

d 

dd 

odd 

OH 

© 

•"* 

P 

•uot^OBay 
niinqoio 

+ 

■H 

4- 

+4 

++ 

+ 
+ 

+ 

+ 

6 

•tnin-o  jay 

^nlom 

© 

NCO-*t>£J 

■* 

t^eg 

OMO 

OO 

<£> 

© 

"3«g 

•snao 

'-'-tflNCO 

— i          ^ 

■* 

rfrert-t* 

c« 

l-:c; 

<M-*<C<I 
CM 

IOC0 

■* 

CO 

•TrnBgxiassBM 
tniuag 

+  I++ 

+ 

■H 

:« 

'S 

M  + 

+ 

- 

1 

o 

02 

ro  m  a:       m 

OQ 

'i°l 

5      5 

© 

©  ©  ©       © 

© 

©  3 

3 
^^ © 

.      C3 

3 

© 

as 
© 

CO 

>-.=-  >.=^ 

>. 

>-.  >i  ^.^  >> 

>, 

>>>> 

c-e-  ^ 

°~    >> 

>. 

>. 

P      «2 

3*     oo 

lO 

<NIN  »       O 

IM 

■*t~ 

X 

X 

iH 

C3 

H 

CM           ,-1 

— 

^-CCO 

— 

rtrt 

CM 

rt 

hH 

CC 

o     5 

.2     G 

f-^-t-C- 

c^ 

e^-s^ 

• 

02   OQ 

< 

C^C^-C^-ff— 

c- 

s^-e^         ^ 

_d 

— -5 

03 

03  03  ,.  m  -*^ 

E-i 

?"o  a 

c3  5   5  3 

3 

S  3  5  3  9 

a 
o 

-    -   - 
C3   C3  ci 

fl   3 
O  O 

ci 

© 

©  o  o  © 

© 

©  ©  ©  ©  c 

>>  >>  >v  >i  a 

S 

©  © 

©  ©  © 

sa 

Q> 

>J 

3     £ 

>1  >)  >>>-. 

>. 

>>>> 

>.>.>. 

>> 

-f« 

cc  cc  *-<  o 

00 

'*r<i-H'*x 

■* 

CM  CM 

OOflH 

ox 

tH 

H 

" 

1-1 

^H  ^H 

>> 

_>•. 

^.2? 

.2±" 

>i 

© 

"0-S"i?"S 

© 

■O  «3 

"^"3 

'■3  a 

© 

o  ©  o  © 

©    S3 

.2 

o 

c 

M 

^  5  5  © 
S'9'2  § 

S3 

©£££ 
.  c  **"  ^"3 

_© 

©*3    S    ©   £-13    g 
odG©.^=3^^ 

©  cS 

"^  o" 

.  3 
-  s 

c9 

©     • 

a— ~^  q, 

>>SV-^ 

CT3 

-.--'  0 

3 

S  Cr  03  =3 

©  ©  ©  o 

>  © 

>  ■'  C   ■'  ©  -r 

>  ©  a  o 

3  IE  - 

>  © 

so? 

42^xsX!'a^,a^3^-2—  K 

a  j^i-3^j2^ 

;  =.-■ 

:  —  ■= 

3  os  3  a 

a  Src! 

S  C3  C3  03v 

^  >.,- 

a  ©  - 

^  03  S 

HHHH 

cH 

"hhhho 

E-i 

&-H 

E-HH 

cqE-i 

0 

H 

« 

H 

«'      (^ 

~ 

< 

/^p^ 

pq 

© 

s 

dd«p; 

W 

W^HaJ0^ 

w 

Q§ 

dwa 

Oo5 

!5 

s 

Kfeffi'j 

>-s 

d^<s^' 

b 

<d 

WWfe 

t5^ 

S 

d 

Z 

OtIihG! 

p^ 

CS  —  t^  O  X) 

00 

o^ 

P.MN 

CMC3 

CO 

ia 

cosh 

C-tNMH 

09 

Tj-I-I 

C3^tC3 

COO 

00 

X 

mmqin 

CM 

o 

i-HOO 

OO 

X 

•<* 

240 


INTRAVENOUS    AND    INTRASPINOUS   TREATMENT       241 

In  the  Munchener  medicinizche  Wochenschrift  of  1913, 
Nos.  36  and  37,  appeared  an  article  describing  the  results 
obtained  by  treating  locally  (intraspinally)  12  patients 
suffering  from  syphilitic  diseases  of  the  nervous  system. 
The  experimenters,  Homer  F.  Swift  and  A.  W.  M.  Ellis, 
conducted  their  observations  at  the  Rockefeller  Institute 
Hospital.    This  method  is  described  in  brief  as  follows: 

The  patient  receives  an  intravenous  injection  of  0.5  gm. 
salvarsan,  in  the  majority  of  cases,  given  in  the  usual  manner. 
One  hour  after  this  administration  enough  blood  is  with- 
drawn from  the  patient's  vein  to  give  at  least  15  c.c.  of 
serum.  The  blood,  obtained  under  aseptic  precautions,  is 
permitted  to  coagulate,  and  is  then  placed  in  the  ice-chest 
overnight.  Next  morning  the  separated  serum  is  very  care- 
fully decanted  off  into  a  centrifuge  tube,  and  permitted  to 
centrifuge  for  about  half  an  hour.  The  clear  supernatant 
serum  is  pipeted  off  from  the  few  red  cells  at  the  bottom,  and 
poured  into  a  graduated  cylinder  up  to  the  12  c.c.  mark, 
and  then  brought  up  to  30  c.c.  by  the  addition  of  sterile  0.9 
per  cent.  NaCl  solution.  This  is  placed  in  a  56°  C.  thermo- 
stat for  thirty  minutes,  to  avoid  danger  of  contamination, 
and  the  mixture  of  serum  and  salt  is  ready  for  intraspinous 
injection. 

The  solution  is  injected  at  body  temperature.  With  the 
patient  lying  on  his  side,  in  bed,  near  the  edge,  the  back  is 
rendered  aseptic  in  the  ordinary  manner,  and  the  area  to  be 
punctured  anesthetized  with  2  per  cent,  sterile  novocain 
solution.  The  lumbar  puncture  needle  is  introduced  in  the 
usual  manner,  and  about  30  c.c.  of  cerebrospinal  fluid  is 
withdrawn,  or  a  quantity  that  will  reduce  the  intraspinous 
pressure  to  about  30  or  40  millimeters.  This  is  gaged  with  a 
3-millimeter  glass  tube  graduated  in  centimeters  and 
millimeters.  When  the  desired  pressure  is  reached,  the  con- 
nection with  the  gage  is  discontinued.  The  serum-salt  mix- 
ture having  been  poured  into  a  Luer  syringe  (large  size) 
carrying  at  the  delivery  point  a  sterile  piece  of  connecting 
rubber  tubing  about  12  inches  long,  this  is  now  attached 
to  the  lumbar  puncture  needle,  taking  care  not  to  introduce 
any  air;  the  mixture  is  then  permitted  to  flow  gently  into  the 

16 


242      SEROLOGY    OF    NERVOUS    AND    MENTAL  DISEASES 

'subdural  space.  The  use  of  the  gage  is  not  essential,  the 
only  requisite  being  that  the  quantity  removed  equal  the 
quantity  introduced;  if  the  patient  complains  of  discomfort, 
the  further  withdrawal  of  fluid  had  best  be  stopped,  and  the 
mixture  introduced  before  30  c.c.  has  been  withdrawn. 

The  table  on  page  240  gives  the  results,  in  part,  of  the 
investigations  carried  out  by  Swift  and  Ellis. 

The  results  are  very  interesting  and  instructive.  The 
most  marked  changes  were  chiefly  in  the  cerebrospinal  fluid. 
The  serum  Wassermann,  however,  was  not  greatly  changed. 
In  the  great  majority  of  instances  the  positive  serum  reac- 
tion remained  positive,  and  only  in  three  instances  was  the 
result  weakly  positive.  Regarding  the  great  diminution  in 
the  pleocytosis,  one  must  be  very  conservative  in  ascribing 
the  fall  in  the  cell  count  entirely  to  the  result  of  the  intra- 
spinous  therapy.  Although  it  is  perhaps  only  partially  respon- 
sible for  the  diminution,  the  possibility  of  diminishing  the  cell 
count  by  the  removal  of  large  amounts  of  fluid,  such  as  is  the 
custom  in  intraspinous  therapy,  must  not  be  lost  sight  of. 
From  the  serologic  point  of  view,  the  cases  of  tabes  corre- 
spond to  the  "Wassermann  fast"  type  described  in  Part 
III  of  this  volume.  Why  the  globulin  content  should  not  be 
influenced  in  the  greater  number  of  instances  is  not  clear, 
in  view  of  the  fact  that  the  cell  count  became,  in  the  majority 
of  cases,  almost  normal.  The  method  of  giving  intraspinous 
injections  was  elaborated  by  Drs.  Swift  and  Ellis,  the  inten- 
tion being  to  bring  to  the  cerebrospinal  circulation  direct 
the  arsenic  contained  in  salvarsan.  The  authors  of  the  com- 
bined method  claim  that  after  giving  intravenous  injections 
alone  hardly  any  arsenic  reaches  the  spinal  fluid. 

THE  " INTENSIVE  INTRAVENOUS"  METHOD 

In  studying  the  chemistry  of  salvarsan  and  its  effects  upon 
microorganisms  more  or  less  closely  related  to  the  spiro- 
chetes of  syphilis,  it  became  apparent  that  when  trypano- 
somes  are  treated  with  small  doses  of  atoxyl,  it  is  possible 
to  render  them  atoxyl-fast.  A  subsequent  dose  of  atoxyl 
large  enough  to  kill  the  non-atoxyl-fast  trypanosomes  will 
have  no  effect  on  the  atoxyl-fast  strain. 


THE    "  INTENSIVE    INTRAVENOUS  "    METHOD  243 

Ehrlich  demonstrated  that  such  a  strain  of  trypanosomes 
is  still  susceptible  to  the  effect  of  arsenophenylglycin.  If 
these  trypanosomes  are  treated  with  minute  doses  of  arseno- 
phenylglycin, a  strain  of  microorganisms  will  be  produced 
that  are  atoxyl  as  well  as  arsenophenylglycin-fast.  This 
strain  of  trypanosomes  is,  however,  promptly  killed  with 
para-amidophenylarsenoxid. 

The  significance  of  the  foregoing  biologic  facts  lies  in  the 
manner  in  which  these  spirillocidal  chemicals  act.  They  all 
contain  arsenic,  and  can  be  attached  to  the  trypanosomes 
by  either  the  amido  (NH2)  or  the  hydroxyl  (OH)  group. 
Other  groups  are  spirillotropic,  such  as  the  glycin  (CH2- 
(NH2)CO)  molecule  of  arsenophenylglycin,  of  which  perhaps 
the  acetic  acid  radicle  plays  the  important  part  of  the  hapto- 
phore  group.  These  facts  must  be  remembered  in  order  to 
form  a  clear  conception  of  what  may  occur  when  patients 
are  treated  with  salvarsan  or  neosalvarsan.  If  the  Treponema 
pallidum  is  capable  of  becoming  salvarsan-fast,  what  should 
be  done,  and  how  can  such  a  phenomenon  be  demonstrated? 
These  questions  can  be  touched  upon  only  superficially, 
and  open  up  a  field  of  experimental  possibilities  that  may, 
in  the  future,  serve  as  a  beacon-light  to  the  exact  scientific 
eradication  of  syphilis.  At  present  one  must  be  content  to 
attempt  the  elaboration  of  what  may  serve  as  a  nucleus  for 
future  workers. 

In  the  Neurological  Institute  and  from  the  service  of 
the  Second  Division  a  method  of  treatment  was  devised 
that  has  given  very  gratifying  results  in  a  comparatively 
short  time — in  some  cases  in  less  than  one  month.  The  results 
secured,  clinically  and  serologically,  were  such  as  to  promise 
much  improvement  in  cases  that  were  previously  treated 
with  salvarsan  without  being  benefited.  By  this  method 
neosalvarsan  is  given  in  0.45  doses  intravenously,  two  days 
being  allowed  to  intervene  between  injections.  Five  injec- 
tions are  given  unless  contraindications  develop.  During  the 
two  intervening  days  the  patient  receives  inunctions  of  mer- 
cury, if  necessary.  Out  of  a  total  of  35,  all  but  one  showed 
improvement  clinically.  Of  these  35,  only  20  presented  them- 
selves for  subsequent  serologic   observation,  and  of   these, 


244      SEROLOGY    OF    NERVOUS    AND    MENTAL    DISEASES 

only  3  patients  retained  their  plus  Wassermann,  these  pa- 
tients being  paretics  in  the  well-advanced  stage.  Of  these  3 
patients,  one  had  a  second  series  of  "intensive  treatment," 
after  which  his  Wassermann  became  negative. 

In  the  treatment  of  diseases  of  the  nervous  system  one 
must  bear  in  mind  that  the  pathologic  process  caused  by 
syphilis  presents  two  phases :  one  is  the  actual  disease,  which 
is  an  exudative  process  of  greater  or  lesser  intensity;  the 
other  is  the  result  of  the  syphilis,  i.  e.,  the  production  of 
degenerative  changes  in  the  nervous  system.  The  therapeu- 
tist must  remember  that  the  degenerative  process  cannot, 
as  the  result  of  treatment,  be  converted  into  the  normal  or 
nearly  normal,  and  it  remains  for  him  to  do  the  best  he 
can  under  the  circumstances — treat  the  exudative  mani- 
festations of  the  disease.  This  treatment  has  been  described 
in  the  third  part  of  this  volume. 

The  evanescent  palsies,  the  pains,  even  the  memory  de- 
fect, the  hand-writing,  and  the  speech  of  the  paretic  may  all 
be  influenced  by  therapy,  which  must,  therefore,  be  consid- 
ered in  those  cases  as  produced  by  an  exudative  and  not  by 
a  degenerative  process.  The  Argyll-Robertson  pupil,  the 
absent  knee-jerks,  and  the  Romberg  symptom  are  the 
manifestations  of  degeneration,  and  are  not,  therefore, 
amenable  to  therapy. 

As  the  changes  that  take  place  in  cerebrospinal,  cerebral, 
or  spinal  lues  are  related  to  a  purely  exudative  pathology,  be 
it  meningitic,  gummatous,  or  endarteritic,  the  results  of 
treatment  are  consequently  better  than  in  tabes  or  in  general 
paresis,  for  in  these  diseases  we  are  confronted  by  degenera- 
tive changes  in  addition  to  the  accompanying  exudation. 

As  the  pleocytosis  is  a  fair  gage  of  the  extent  of  the  exuda- 
tion, the  method  of  treatment  that  will  render  20  or  30  cells 
normal  as  well  as  negativate  the  positive  Wassermann  is  of 
greater  utility  than  a  method  that  can  only  reduce  the  cell 
count  of  those  cases  that  present  a  pleocytosis  of  100  or  more. 
The  treatment  that  will  convert  a  positive  Wassermann  into 
a  negative  reaction  in  a  patient  with  general  paresis  has 
effected  a  better  result  than  a  method  that  can  accomplish  this 
only  in  a  case  of  ordinary  tabes  or  cerebrospinal  syphilis,  with- 


THE        INTENSIVE    INTRAVENOUS        METHOD 


245 


out  being  able  to  influence  the  former  disease.  The  author 
consequently  considers  the  "intensive  method"  of  treatment 
a  distinct  advantage  over  other  methods  of  administering 
salvarsan  or  neosalvarsan,  as  it  shows  results  clinically  and 
serologically  superior  to  any  that  have  come  to  his  knowledge 
up  to  the  present  time  (February,  1914).  The  following 
table  was  compiled  by  Dr.  Stephenson,  to  whom  the  author 
is  indebted  for  its  presentation: 

RESULTS  OF   "INTENSIVE  TREATMENT" 


No. 

Name. 

Diagnosis. 

S.  w. 

F.  W. 

Gl. 

Pl. 

Therapy. 

S.  W. 

F.  W. 

Gl. 

Pl. 

1. 

O.G. 

Tabes. 

+ 

+ 

+ 

34 

1  series. 







10 

2. 

Ham. 

Tabes. 

+ 

+ 

+ 

27 

1  series. 

— 

— 

— 

0 

3. 

Kal. 

Tabes. 

+ 

+ 

+ 

77 

1  series. 

— 

— 

— 

0 

4. 

Mur. 

Cerebro- 

spinal lues. 

+ 

+ 

+ 

117 

3  inject. 

— 

— 

— 

28 

5. 

Sau. 

Cerebro- 

spinal lues. 

+ 

+ 

+ 

93 

1  series. 

— 

— 

— 

48 

6. 

Sch. 

Tabo- 

paresis. 

+ 

+ 

+ 

40 

1  series. 

W.+ 

W.+ 

W.+ 

11 

7. 

Man. 

Tabo- 

paresis. 

+ 

+ 

+ 

70 

1  series. 

— 

— 

— 

16 

8. 

Bra. 

Paresis. 

+ 

+ 

+ 

34 

1  series. 

+ 

+ 

+ 

16 

9. 

Kin. 

Paresis. 

+ 

+ 

+ 

63 

1  series. 

+ 

+ 

W.-f 

60 

10. 

Fur. 

Paresis. 

+ 

+ 

+ 

32 

2  series. 

Three 
months 

apart. 

W.4- 

W.+ 

W.+ 

32 
34 

The  clinical  reports  show  that  all  the  patients  but  patient 
No.  8  showed  improvement.  With  the  exception  of  the 
paretic  cases,  the  other  syphilogenous  nervous  diseases 
treated  all  showed  serologic  improvement.  Paretic  No.  10 
showed  an  improvement  in  his  serology  after  a  second  series 
of  injections.  Considering  the  limitations  that  the  treatment 
of  such  diseases  are  subject  to,  the  results  are  as  good  as  can  be 
expected  at  present.  The  possibility  of  rendering  the  trypan- 
osomes  resistant  to  one  drug,  and  being  able,  at  the  same 
time,  to  destroy  them  with  an  arsenic-carrying  chemical  sub- 
stance possessing  a  different  spirillotrophic  haptophore  group, 
was  spoken  of  on  a  previous  page.  This  phenomenon  is  de- 
scribed in  connection  with  the  various  methods  of  therapy  so 


246      SEROLOGY   OF   NERVOUS   AND    MENTAL    DISEASES 

as  to  impress  upon  the  therapeutist  the  possibility  of  its 
occurrence  in  the  human  organism,  and  with  the  Trepo- 
nema pallidum. 

The  author  had  the  opportunity  of  treating  patients  with 
neosalvarsan  by  the  "intensive  method,"  and  in  some  cases 
the  positive  Wassermann  could  not  be  rendered  negative. 
The  possibility  of  the  existence  of  a  neosalvarsan-fast  strain 
of  microorganisms  occurred  to  the  author,  and  gradually 
increasing  doses  of  salvarsan  were  given  intravenously  in  a 
second  series:  the  initial  dose  given  was  0.4  gm.;  after  two 
days'  interval  0.45  gm.  was  given,  and  so  on  until  0.6  gm. 
was  injected.  During  the  salvarsan-free  days  the  patients 
received  two  inunctions  of  mercury  daily.  The  four  cases 
thus  treated,  who  all  presented  a  positive  Wassermann  before 
the  salvarsan  series,  all  gave  a  negative  Wassermann  reaction 
in  the  serum:  one  after  two,  one  after  four,  and  the  remaining 
two  after  five  injections.  One  of  the  patients  improved 
sufficiently  to  enable  him  to  return  to  business.  All  patients 
were  clinically  paretics. 

The  entire  subject  of  treatment  of  the  syphilogenous 
nervous  diseases  with  salvarsan  or  neosalvarsan  is  to  be 
regarded  as  still  in  the  experimental  stage.  One  of  the  facts 
established  by  the  modern  therapeutist  is  that  mercury  can- 
not be  dispensed  with  no  matter  how  brilliant  the  success 
that  attends  the  treatment  with  the  newer  remedies.  Sal- 
varsan and  substances  allied  to  salvarsan  accomplish  definite 
purposes,  which,  although  resembling  the  action  of  mercury 
to  some  extent,  still  do  not  possess  all  the  curative  qualities 
for  which  mercury  is  known,  so  that  the  greatest  success 
will  be  obtained  when  the  old  and  the  new  remedies  are 
combined.  Enough  has  been  written  regarding  the  subject 
to  justify  the  combined  treatment  of  syphilitic  nervous 
diseases,  the  mercury  being  used  in  the  form  of  inunctions, 
and  the  neosalvarsan  being  administered  intravenously. 
If  the  desired  results  are  not  secured  after  the  patient  has 
had  a  treatment-free  period  of  two  weeks,  it  is  advisable  to 
institute  a  series  of  salvarsan  injections,  as  previously  sug- 
gested, and,  in  addition,  prescribe  inunctions  of  mercury 
twice  a  day.     This  method  usually  negativates  the  pre- 


POST-SALVARSAN    MANIFESTATIONS  247 

viously  positive  Wassermann  in  the  serum  and  fluid,  and, 
as  a  rule,  is  followed  by  clinical  improvement.  If  the  patient 
does  not  respond  to  this  strenuous  therapy,  an  intraspinous 
injection  may  be  given  tentatively,  and  repeated  at  definite 
intervals  until  the  Wassermann  reaction  becomes  negative. 
As  the  negativating  powers  of  the  intraspinous  method  are 
not  very  great,  it  is  sometimes  better  to  permit  the  patient 
to  retain  his  positive  serum  Wassermann  without  treatment, 
so  long  as  his  clinical  status  is  good  enough  to  justify  such 
a  procedure.  A  watchful  eye  must,  however,  be  kept  on  the 
serologic  status  of  such  patients,  and  any  return  of  a  pleo- 
cytosis  or  the  return  of  an  excess  of  globulin  is  to  be  promptly 
met  by  a  series  of  injections. 

POST-SALVARSAN  MANIFESTATIONS 

Local  Reaction  From  Intramuscular  and  Intravenous 
Injections. — Any  irritating  effect  produced  by  salvarsan 
can  be  detected  by  the  subjective  complaints  of  the  patient 
and  the  objective  signs  at  the  site  of  the  injection.  One  of  the 
many  necroses  described  in  the  literature  as  following  the 
use  of  the  drug  is  pictured  in  Fig.  20.  A  lesion  produced 
by  salvarsan  heals  with  great  difficulty;  the  author  had  a 
slight  scratch  on  a  finger  that  was  brought  in  contact  with  the 
drug;  this  remained  painful  and  did  not  heal  for  two  weeks. 
Although  the  irritating  properties  of  the  drug  may  be  neu- 
tralized by  oil,  paraffin,  etc.,  instances  are,  nevertheless, 
recorded  in  which  necroses  occurred,  and  many  cases  of 
painful  swelling  are  seen. 

The  improper  administration  of  the  intravenous  injection — 
i.  e.,  the  drug  being  driven  into  the  perivenous  tissues — re- 
sults in  reactions  similar  to  the  intramuscular  manifestations, 
and  in  some  instances  sloughing  may  follow.  If  an  improper 
injection  has  been  given,  this  becomes  manifest  at  once,  as 
the  perivenous  salvarsan  infiltration  makes  itself  felt  imme- 
diately. Small  infiltrations — of  a  few  drops  only — will 
result  in  an  arm  that  will  be  painful  for  a  few  days  only 
and  a  black-and-blue  discoloration.  Such  an  arm  should  not 
receive  another  injection  until  the  pain  and  discoloration 
have  disappeared.    In  these  cases  it  may  be  that  the  vein  will 


248      SEROLOGY    OF    NERVOUS   AND    MENTAL    DISEASES 

become  thrombosed  and  rendered  useless  for  an  inch  or  more. 
"Where  many  injections  are  necessary,  it  is  evident  that  con- 
servation of  the  patient's  veins  is  quite  important.  Many 
patients  display  veins  of  which  only  one  or  two  are  suitable 
for  receiving  the  treatment.  A  black-and-blue  discoloration 
is  sometimes  produced  by  an  extravasation  of  blood;  this  is, 
however,  painless,  and  never  causes  thrombosis. 

Neurotic  patients  at  times  complain  of  pain  in  the  axilla; 
this  lasts  only  for  a  short  time, — an  hour  or  two, — and 
disappears  without  special  treatment. 

General  Reactions. — (a)  Headache. — The  headache  that 
follows  the  injection  of  salvarsan  is  frequently  not  so  much 
the  result  of  the  drug  as  due  to  the  nervousness  of  the 
patient.  Neurotic  headaches  often  occur  during  the  injec- 
tion of  the  drug,  and  usually  in  patients  who  are  getting  their 
first  salvarsan  treatment.  In  cases  of  cerebral  syphilis, 
where  headaches  are  habitual,  an  aggravation  of  this  symp- 
tom is  an  unpleasant  accompaniment  of  the  therapy,  it 
being  impossible  to  decide  whether  the  pain  is  due  to  an 
increase  in  the  exudative  luetic  process  or  to  causes  that 
bear  no  relation  to  the  treatment,  such  as  constipation, 
anxiety,  and  an  empty  stomach.  The  headache  due  to  an 
aggravation  of  the  cerebral  process  usually  occurs  in  from 
ten  to  twenty-four  hours  after  the  administration  of  the 
drug,  whereas  a  headache  due  to  other  causes  manifests 
itself  much  earlier. 

For  this  casual  occurrence  of  headache  none  of  the  coal- 
tar  remedies  ought  to  be  prescribed,  and  it  is  better  to  wait 
or  to  treat  the  causal  condition  if  any  is  found  to  exist. 

(6)  Although  very  rarely  a  distressing  symptom,  one  is 
sometimes  called  upon  to  treat  nausea.  A  little  hot  water 
every  ten  minutes,  given  largely  for  its  psychic  effect,  is  at 
times  sufficient  to  relieve  the  condition.  Some  patients  dis- 
play this  symptom  every  time  they  are  injected,  whereas 
others,  again,  manifest  it  only  as  a  result  of  many  short  in- 
terval treatments,  as  when  a  series  is  given. 

(c)  Vomiting. — This  symptom  will  at  times  require  a 
hypodermic  injection  of  |  grain  of  morphin  for  its  relief. 
Hot  tea  is  also  useful.  The  vomiting,  as  a  rule,  does  not  last 
long,  and  need  give  the  physician  no  great  concern. 


POST-SALVARSAN    MANIFESTATIONS  249 

(d)  Diarrhea. — This  symptom  may  at  times  prove  quite 
troublesome,  although  it  is  never  of  an  alarming  nature. 
The  complication  is  perhaps  best  met  by  the  use  of  pro- 
phylactic measures,  such  as  thorough  clearing  of  the  bowel 
before  treatment  by  mild  catharsis,  or  by  administering  a 
small  quantity  of  Epsom  salts  an  hour  after  giving  the 
intravenous  injection.  These  diarrheas  occur  in  patients 
who,  as  a  rule,  are  not  subject  to  flux,  and  may  even  be  seen 
in  patients  who  are  habitually  constipated.  If  the  measures 
suggested  fail  and  the  diarrhea  is  becoming  very  distressing, 
one  is  justified  in  resorting  to  the  ordinary  methods  for  its 
relief,  such  as  morphin  and  atropin  or  bismuth  and  chalk. 
Clearing  the  lower  bowel  by  means  of  an  enema  at  times 
has  the  desired  effect. 

(e)  Chills  and  Fever. — The  chills  and  fever  that  formerly 
occurred  immediately  after  injections  of  salvarsan  are  very 
rarely  encountered  at  the  present  time,  since  freshly  dis- 
tilled water  is  employed  in  the  preparation  of  the  drug. 
They  are  still  less  frequently  seen  when  neosalvarsan  is 
used.  The  latter  drug  gives  rise  to  fewer  manifestations 
than  does  the  older  salvarsan,  the  same  precautions  being 
used.  In  the  author's  experience  a  hot-water  bottle  and  a 
cup  of  hot  tea  are  all  that  are  required  for  the  relief  of  this 
condition.  The  fever  is  rarely  high,  although  cases  are  on 
record  in  which  a  temperature  of  104°  and  even  105°  F. 
was  observed.  As  previously  stated,  these  complications  are 
becoming  fewer  with  a  better  understanding  of  the  technic, 
a  more  careful  selection  of  patients,  and  the  adoption  of 
proper  and  timely  precautions. 

The  reaction  is  usually  accompanied  by  a  trace  of  albumin, 
and  rarely  by  a  hyaline  cast  or  cylindroid  in  the  urine.  Where 
the  renal  reaction  is  more  severe,  one  must  be  very  careful 
in  using  the  drug  again,  as  a  severe  nephritis  may  develop. 

(/)  Skin  Manifestations. — Morbilliform  and  scarlatiniform 
eruptions  may  follow  the  use  of  neosalvarsan  or  salvarsan 
in  from  two  to  forty-eight  hours,  or  they  may  appear  as  late 
as  a  week  or  ten  days  after  the  last  injection  was  given. 
The  reaction  is  chiefly  a  toxic  manifestation,  and  only  partly 
a  reaction  of  a  syphilitic  organism  to  the  introduction  of 


250      SEROLOGY   OF    NERVOUS    AND    MENTAL   DISEASES 

arsenic.  These  dermatologic  manifestations  are  usually 
accompanied  by  considerable  itching,  more  or  less  pro- 
nounced edema,  and  frequently  by  fever.  The  temperature 
may  rise  to  104°  or  even  105°  F.  For  this  complication, 
eliminative  therapy  is  recommended,  together  with  local 
applications  of  zinc  stearate.  As  the  reactions  are  at  times 
very  severe,  all  the  precautions  necessary  in  acute  illnesses 
are  to  be  observed  in  these  cutaneous  post-salvarsan  mani- 
festations; these  include  attention  to  diet,  elimination,  and 
stimulation. 

The  Herxheimer  Reaction. — This  very  interesting  post- 
salvarsan  manifestation  will  be  discussed  at  length  from 
the  neurologist's  point  of  view,  the  studies  of  Milian  being 
followed  in  detail: 

The  Herxheimer  reaction  is  an  inflammatory  reaction  pro- 
duced in  syphilitic  tissues  through  the  influence  of  specific 
treatment.  This  reaction  may  manifest  itself  not  only  after 
the  intravenous  administration  of  salvarsan  or  neosalvarsan, 
but  also  after  the  injection  of  mercury  salicylate,  calomel, 
sodium  cacodylate,  etc.  Every  luetic  lesion,  whether  cuta- 
neous, mucous,  or  visceral,  is  capable  of  reacting  in  such 
manner.  We  may  have  a  liver  reaction  or  a  renal  complica- 
tion, with  transient  icterus  in  the  former  and  albuminuria 
in  the  latter.     The  nervous  system  responds  similarly. 

The  occurrence  of  the  Herxheimer  reaction  has  been  vari- 
ously explained  by  different  authorities;  e.  g.,  liberation  of  a 
syphilis-endotoxin  causing  a  hyperemia  (Thalmann);  exci- 
tation of  the  treponema  by  an  insufficient  dose  of  the  drug 
(Ehrlich,  Iversen,  Wechselmann,  Loeb,  etc.).  Individual 
irregularities  in  the  vascular  tonus  (Frankel  and  Grouven). 
Mercury  and  salvarsan  act  in  a  manner  similar  to  tuberculin 
(Julius  Baum).  The  reaction  is  comparable  to  the  tuber- 
culin effect  in  lupus  (Richard  Kalb). 

The  theory  regarding  the  reaction  that  has  gained  the 
widest  credence  is  that  expressed  by  Ehrlich,  Iversen, 
Wechselmann,  Loeb,  etc. 

Symptomatology. — The  cutaneous  reaction  is  manifested 
by  an  inflammatory  train  of  symptoms  giving  rise  to  edema, 
redness,  pain,  and  even  to  fever,  these  usually  following 


POST-SALVARSAN    MANIFESTATIONS  251 

the  first  injection.  The  mucous  patches  react  in  a  manner 
similar  to  the  cutaneous.  The  gummatous  formations  be- 
come swollen,  may  ulcerate,  and  are  capable  of  producing 
considerable  exudation.  This  is  particularly  important  to 
the  neurologist,  who  may  have  to  consider  such  a  reaction 
in  a  cerebral  gumma  before  advising  salvarsan  therapy. 

The  viscera  involved  in  the  syphilitic  process  react  in  a 
manner  similar  to  the  cutaneous  manifestations;  if  the  liver 
is  affected  an  angiocholitis  sets  in,  and  bile-products  appear 
in  the  urine.  The  author  has  observed  that  in  cases  where 
the  patient  had  an  alcoholic  history  as  well  as  lues  of  the 
nervous  system,  the  injection  of  salvarsan  would  give  an 
intense  reaction  with  Ehrlich's  dimethyl-amido-benzaldehyd 
solution.  In  some  instances  the  reaction  is  quite  severe,  and 
is  to  be  regarded  as  a  toxic  manifestation  of  the  salvarsan 
injection.  The  symptoms  are  more  pronounced,  there  being 
pains  in  the  limbs,  depression,  restlessness,  lassitude,  and 
rapid  pulse.  Three  or  four  days  later  the  face  becomes  con- 
gested and  red,  the  redness  being  not  of  the  usual  febrile 
color  or  of  the  scarlet  red  previously  spoken  of,  but  of  a 
brick-like  hue,  somewhat  resembling  the  red  paint  used 
by  Indians.  At  the  same  time  the  conjunctivae  become 
very  much  injected,  and  pinhead-sized  extravasations  may 
occur  in  the  sclera.  The  urine  is  high  colored,  and  shows  a 
marked  albumin  reaction.  On  the  following  day  the  urine 
becomes  almost  green  in  color,  and  at  times  even  black,  and 
gives  the  reaction  for  bile-pigments.  The  temperature  is 
usually  very  high,  and  the  general  condition  of  the  patient 
is  very  poor.  On  the  sixth  day  the  redness  of  the  face  is 
replaced  by  a  true  icteric  color,  the  conjunctivae  also  becoming 
yellow. 

The  liver  is  small;  the  spleen  is  large;  the  feces  are  of  an 
ashen  hue.  The  patient  becomes  extremely  emaciated  and 
very  weak.  The  symptoms  gradually  abate,  and  a  crisis 
occurs  at  the  end  of  about  two  weeks,  when  the  patient 
begins  to  void  large  quantities  of  urine. 

The  Nervous  System. — The  nervous  system  is  more  lastingly 
involved  in  a  Herxheimer  reaction  than  is  any  other  portion 
of  the  body  affected  by  such  a  process.    This  is  particularly 


252      SEROLOGY  OF    NERVOUS    AND    MENTAL    DISEASES 

the  case  where  the  cranial  nerve  traverses  a  rigid  bony 
canal,  and  where  opportunities  for  compression  are  greatest. 
The  facial  paralyses  that  follow  a  salvarsan  injection  are 
due  to  a  Herxheimer  reaction  that  manifests  itself  in  the 
Fallopian  aqueduct.  The  vestibular  and  cochlear  branches 
of  the  eighth  nerve  are  affected  for  a  similar  reason.  The 
involvement  of  the  vestibular  branch  is  frequently  the  cause 
of  the  vomiting  and  vertigo  that  sometimes  occur.  A  Meniere 
phenomenon  may  occur  after  a  salvarsan  injection. 

In  cases  of  cerebral  lues  the  reaction  usually  manifests 
itself  in  the  form  of  severe  headaches.  In  other  cases, 
where  focal  signs  exist,  the  reaction  assumes  an  exudative 
character,  producing  irritative  manifestations  and  paralyses. 
These,  as  a  rule,  are  transient  in  character,  and  usually 
appear  after  the  second  injection.  In  patients  with  tabes 
the  intravenous  injection  of  salvarsan  or  neosalvarsan  pro- 
duces a  Herxheimer  reaction  characterized  by  severe  pains, 
which  appear  in  from  one-half  to  one  hour  after  the  injection 
is  given.  The  pains  may  last  for  forty-eight  hours  and  may 
not  disappear  entirely  for  three  or  four  days.  These  painful 
reactions  require  vigorous  morphin  therapy  until  the  pinch- 
ing exudation  affecting  the  posterior  roots  disappears. 
These  pains  may  at  times  be  checked  by  giving  another 
smaller  injection  of  salvarsan.  The  so-called  provocative 
positive  Wassermann  reaction  must  also  be  considered  as  a 
Herxheimer  phenomenon. 

For  purposes  of  differentiation  between  a  Herxheimer 
reaction  and  a  reaction  due  to  arsenic  intolerance,  the 
following  table  of  Milian  is  offered: 

Herxheimer  Reaction.  Reaction  Due  to  Intolerance. 

1.  Reaction  becomes  less  marked      1.  Whether  the  same  dose  is  given 

with  repeated  injections.  or  a  larger  or  a  smaller  one, 
This  may  in  some  cases  re-  the  subsequent  injection  pro- 
quire  more  than  two  or  three  duces  a  more  marked  toxic 
injections.  effect. 

2.  As  the   syphilis   improves  the  2.  Irrespective    of    the    improve- 

reactions  become  less  marked.  ment  in  the  syphilis,  the  toxic 

manifestations     remain     the 
same. 

3.  The  reaction  is  observed  most     3.  Occurs  regardless  of  the  nature 

frequently  in  syphilis  of  the  of  syphilitic  involvement, 

nervous  system. 


THE   AMINO-NITROGEN   CONTENT   OF   SERA  253 

4.  The  reaction  is  usually  accora-     4.  Is  not  accompanied  by  a  pleo- 

panied     by     a     pleocytosis.  cytosis,  nor  is  the  cell  count 

Where  a  cellular  increase  was  changed    if    it    was    present 

present  before  the  injection,  before  the  injection, 
this  is  markedly   augmented 
after. 

5.  The  Wassermann  reaction  re-  5.  The  Wassermann  reaction  be- 

mains  unchanged  or  becomes  comes  negative  or  disappears, 

more  intensely  positive. 

6.  The  injection  of  adrenalin  has      6.  An    injection    of    a    sufficient 

no    effect    whatever    on    the  quantity  of  adrenalin  is  cap- 

reaction,  able    of   diminishing   the   in- 

tensity in  a  large  number  of 
cases  due  to  intolerance. 

7.  The  phenomena  attending  the      7.  The  reaction  differs  from  any 

reaction  possess  to  a  certain  symptom    usually    found    in 

degree  the  characteristics  of  syphilitic  phenomena, 

syphilitic  manifestations. 


THE  AMINO   (NH2)   NITROGEN  CONTENT  OF  SERA 

The  results  obtained  with  the  quantitative  estimation  of 
the  alpha  NH2  nitrogen  of  the  aliphatic  acid  group  of  sera 
from  syphilitic  and  non-syphilitic  patients  make  it  desirable 
to  insert  here  a  brief  description  of  this  chemical  test: 

Rationale. — On  a  previous  page  the  spirillotropism  of 
salvarsan  and  neosalvarsan  was  spoken  of;  It  was  demon- 
strated that  there  are  certain  chemical  groups  that  act  as 
haptophores  (anchoring  or  prehensile),  which  render  the  two 
drugs  of  great  therapeutic  importance.  These  groups  may 
be  the  OH  or  the  NH2  or  the  (CH2)OSNa  side-chains  of  sal- 
varsan or  neosalvarsan.  The  fact  that  the  Treponema  palli- 
dum anchors  these  drugs  through  these  chemical  side- 
chains  led  the  author  to  seek  to  ascertain  the  effect,  if  any 
occurred,  of  the  sojourn  of  the  treponema  in  the  human  body 
upon  the  chemical  constituents  of  the  serum  having  similar 
side-chains.  The  many  chemical  substances  forming  the 
blood-serum  molecule  are  chiefly  amino-acids,  of  which  the 
simpler  ones  are  the  following: 

Alanin,  or  alpha-amino-propionic  acid: 


CH3 

I 
CH(NH2) 

OOH 


A 


254      SEROLOGY    OF   NERVOUS    AND   MENTAL  DISEASES 

Leucin,  or  alpha-amino-isobutyl-acetic  acid : 
CIL        CH, 


CH 

I 
CH2 

CH(NH2) 

COOH 

Asparaginic  acid,  or  amino-succinic  acid: 

COOH 

CH(NH2) 

I 
CH2 

COOH 

Tyrosin,  or  para-oxyphenyl-alpha-amino-propionic  acid: 

OH 

I 

/C\ 
HC         CH 

HC         CH 

I 
CH2 

CH(NH2) 

COOH 

Glutaminic  acid,  or  alpha-amino-glutaric  acid: 

COOH 

I 
CH(NH2) 

I 
CH2 

I 
CH2 

I 
COOH 

The  tropism  that  exists  between  a  certain  drug  and  a 
given  microorganism  was  extensively  studied  by  Ehrlich 
and  his  pupils,  and  resulted  in  the  formulation  of  a  hypoth- 
esis, previously  referred  to;  i.  e.,  "Corpora  non  agunt  nisi 
fixata."     The  possibility  of  analyzing  quantitatively  the 


THE    AMINO-NITROGEN    CONTENT    OF    SERA  255 

alpha-amino-nitrogen  of  the  aliphatic  acid  radicle  of  the 
amino-acids  composing  the  serum  molecule  was  introduced 
by  Donald  van  Slyke,  whose  method  will  here  be  given: 
Technic. — 

(a)  Reagents:    (1)  Glacial  acetic  acid. 

(2)  300  grams  sodium  nitrite  in  1000 
c.c.  of  distilled  water. 

(3)  Potassium  permanganate,  50 
grams;  potassium  hydoxid,  25 
grams,  dissolved  in  1000  c.c.  of 
distilled  water. 

(6)  Apparatus:  This  consists  of  a  special  receptacle 

for  the  liberation  of  the  amino-nitrogen  from 

the  serum  to  be  analyzed,  and  is  provided  with 

four  stop-cocks. 

A  measuring  buret  with  the  top  1^  c.c.  graduated 

into  hundredths. 
A  200  c.c.  leveling  water  bulb,  pear  shaped. 
A  Hempel  pipet,  and  a  connecting  glass  tube. 
Preparation  of  Apparatus  for  Use. — Having  joined  the 
various  parts  of  the  apparatus,  as  shown  in  the  accom- 
panying illustration  (Fig.  31),  fill  the  Hempel  pipet  with 
the  potassium   permanganate   solution    so  that   the  lower 
bulb  will  be  entirely  full  and  the  upper  one  only  half-full. 

Fill  the  pear-shaped  water  reservoir  with  distilled  water; 
turn  stop-cock  2  so  that  it  communicates  with  the  waste  and 
with  the  measuring  buret  only;  in  other  words,  with  the 
short  limb  of  the  bore  in  the  stop-cock  pointing  to  the  buret. 

Turn  stop-cock  3  so  that  it  communicates  with  the  cross 
tube  of  the  nitrogen-separating  receptacle  b.  Raise  the  water 
bulb  slightly  higher  than  the  buret,  pour  in  sufficient  water 
to  fill  the  buret,  and  leave  the  water  bulb  about  half-full. 
Turn  cock  3  neutral.    Lower  the  water  bulb. 

Now  turn  cock  3  so  that  it  communicates  with  the  Hempel 
pipet.  The  permanganate  will  flow  into  the  buret.  Turn 
cock  3  neutral.  Quickly  communicate  cock  3  with  the  waste, 
raise  the  water  bulb,  and  rid  the  buret  of  the  permanganate. 
Turn  cock  3  neutral  again,  and  cock  2  so  that  it  communi- 
cates with  the  waste,  but  not  with  the  buret,  i.  e.,  with  the 


256   SEKOLOGY  OF  NERVOUS  AND  MENTAL  DISEASES 


short  limb  of  the  bore  to  the  left,  pointing  to  the  nitrogen- 
liberating  receptacle  b.     The  apparatus  is  now  ready  for  use. 

As  the  sodium  nitrite  is  rarely  absolutely  pure,  it  is  there- 
fore necessary  to  perform  a  preliminary  test  to  ascertain  the 
amount  of  non-absorbable  gas  present  in  the  chemical. 

Turn  stop-cock  1  neutral  and  pour  into  a  glacial  acetic 
acid  up  to  mark  10.    Turn  cock  1  so  that  the  acid  will  flow 

A 


Fig.  31. — Schematic  diagram  of  the  apparatus. 

into  b,  and  turn  stop-cock  1  again  neutral.  Pour  into  a 
enough  of  the  nitrite  solution  to  fill  it  up  to  mark  40,  and  per- 
mit it  to  flow  into  b  by  turning  the  cock  1.  During  this 
operation  cocks  4  and  5  must  be  in  the  neutral  position. 
As  soon  as  all  the  sodium  nitrite  solution  is  out  of  part  a 
cock  1  is  turned  neutral  and  the  motor  started.    The  com- 


Fig.  32. — Entire  apparatus  assembled  for  permanent  use. 


THE    AMINO-NITROGEN   CONTENT   OF   SERA  257 

bination  of  glacial  acetic  acid  and  the  nitrite  solution  causes 
a  rapid  formation  of  NO  gas,  which  forms  the  brownish 
fumes  that  escape  through  the  waste.  The  motor  shakes  the 
gas-separating  receptacle  and  fills  the  entire  apparatus 
with  NO  gas,  driving  off  the  air  present  in  the  apparatus. 
Having  effected  the  filling  of  the  apparatus  with  NO  gas, 
the  motor  is  stopped,  and  stop-cock  1  is  opened  again. 
Now  turn  stop-cock  2  in  the  neutral  position,  pointing  with 
the  short  limb  of  the  bore  upward,  and  start  the  motor  again. 
This  causes  the  liquid  to  rise  gradually  into  part  a,  and 
when  it  reaches  mark  40  the  motor  is  stopped  and  cock  1 
turned  neutral.  The  stop-cock  3  is  turned  so  that  it  com- 
municates with  the  cross  tube  from  the  gas-liberating  part; 
this  causes  the  water  in  the  buret  to  fall  4  or  5  inches,  which 
is  caused  by  the  NO  in  b. 

The  apparatus  is  now  ready  either  for  the  determination 
of  the  amount  of  amino-nitrogen  in  the  serum  or  for  the 
correction  of  the  nitrite  solution. 

Correction  of  the  Nitrite  Solution.— With  the  apparatus  in 
the  position  just  outlined,  pour  10  c.c.  of  slightly  warmed 
distilled  water  into  part  c  of  the  apparatus,  and,  by  gently 
turning  stop-cock  4,  allow  the  water  to  flow  into  b,  being 
careful  not  to  permit  the  least  amount  of  air  to  enter  com- 
partment b.  Stop-cock  4  is  turned  neutral,  and  the  motor 
started.  The  shaking  is  continued  for  exactly  five  minutes, 
during  which  time  the  gases  formed  lower  the  water  column 
in  the  buret.  At  the  end  of  five  minutes'  shaking  stop  the 
motor,  and  after  waiting  two  minutes  open  stop-cock  1, 
permitting  the  fluid  in  a  to  empty  into  b,  thus  driving  all  the 
gas  into  the  buret,  d.  Do  not  permit  any  of  the  fluid  to  flow 
into  the  buret.  Having  driven  over  all  the  gas,  turn  cock  3 
into  the  neutral  position.  Raise  the  water  bulb  above 
the  buret,  and  turn  cock  3  so  that  it  communicates  with  the 
Hempel  pipet.  This  causes  the  gas  to  flow  into  the  Hempel 
pipet,  during  which  the  apparatus  must  be  watched  closely, 
as  the  NO  gas  may  not  be  absorbed  as  rapidly  as  it  flows 
into  the  permanganate  solution;  it  is,  therefore,  necessary 
to  shake  the  pipet  occasionally,  a  proceeding  that  is  required 
more  often  as  the  permanganate  solution  ages.    The  solution 

17 


258      SEROLOGY   OF   NERVOUS   AND    MENTAL   DISEASES 

may  be  used  for  about  a  dozen  tests,  when  it  ought  to  be  re- 
placed with  fresh  solution. 

Having  driven  over  all  the  gas  as  well  as  a  little  distilled 
water  (about  0.5  c.c.),  stop-cock  3  is  turned  neutral  and  the 
water  bulb  lowered.  Shake  the  Hempel  pipet  vigorously 
for  two  minutes,  and  then  open  cock  3  again,  so  that  the 
permanganate  will  flow  over  to  the  buret.  Having  collected 
the  gas  over  the  water,  cock  3  is  turned  neutral  again, 
and  the  amount  of  gas  present  is  ascertained.  Some  samples 
of  nitrite  solution  give  as  much  as  0.4  c.c.  of  unabsorbable 
gas,  a  fact  which  must  be  taken  into  consideration  when  de- 
termining the  amount  of  amino-nitrogen  present  in  sera. 
The  amount  of  impurity  in  the  nitrite  is  known  as  the  cor- 
rection number. 

Testing  Sera  for  the  Amino-nitrogen. — To  perform  this  test 
2.5  c.c.  of  the  patient's  serum  is  placed  in  an  Erlenmeyer  flask 
and  precipitated  with  25  c.c.  of  95  per  cent,  alcohol.  This 
is  allowed  to  remain  at  room  temperature  overnight,  and 
the  next  morning  it  is  filtered.  The  filtrate  is  collected  in  a 
porcelain  dish,  and  evaporated  over  a  water-bath,  being 
careful  not  to  secure  complete  dryness.  Dissolve  the  mass 
in  about  10  c.c.  of  boiling  distilled  water,  when  it  is  ready  for 
the  determination  in  the  van  Slyke  apparatus. 

The  process  of  determining  the  amino-nitrogen  in  the 
serum  is  the  same  as  that  followed  for  the  determination  of 
the  impure  gas  in  the  nitrite  solution,  the  dissolved  evapor- 
ated filtrate  taking  the  place  of  the  water  poured  into  c. 
The  calculation  is  made  according  to  the  table  compiled  by 
Gattermann,  in  his  book/Traxis  des  organischen  Chemikers," 
ninth  edition.  The  entire  reaction  depends  upon  the  chem- 
ical fact  that  aliphatic  amino-groups  react  with  nitrous 
acid  according  to  the  following  equation: 

RNH2    +    HN02     =     ROH     +    H20     +    N2 

The  nitrous  acid  decomposes  with  the  formation  of  NO. 
This  NO  is  made  use  of  in  this  reaction  to  drive  off  all  the  air 
from  the  apparatus.  Later.it  is  completely  absorbed  by  the 
permanganate  solution,  and  the  gas  obtained  in  the  buret  is 
the  correction  number  together  with  the  amino-nitrogen  in 
the  patient's  serum. 


THE    AMINO-NITROGEN    CONTENT    OF   SERA 


259 


n- 

E  H 

o> 

tt  :r 

B 
c 

a  B 

■o 

5 
a 

p- 

•< 

<"ra 

p 

clb> 

u-rr 

UP 

<<   <t> 

SLB 
o-B 


5  p 

3  S1 


C  2. 

to  c*- 

5.3' 


WtOlObOtGtCtOtNDlOtObGl-'l—l-'l—  >—  >— •  H-  >— ■ 


£H 


oioiocnooH-wa)cDts3^^iQiooic»ocoaiOoto 
OCuOOOOOitnCnOCntnOCnCnOOiOUiOoo 

01OO1010101OOO010001OO01001O01 
OibiOiOiOiUiCnCJiOiCJiCnCncnCTimCTiOiCnOiC^—J 

tOtOCra00i-'>**Oi<OtJCn~J©COCN00i-'WCT>00>->to 
OOOOOOOiOitnOOitnOtnUiOOiOOiO 


tOCnOOi-'i^MOtOOiOOi-'OOOlcOi-'^ascDtO^-OJ 
OOOOOOOO1O1OOO1OOO1OO1O1OO1 

OiOibiCnCnOtCnCnoiCnCnCncnCnCncnCnUiO'OKI 

W0ic0l>3Oi00i-'hf»-~ay3tGCn00Owm00>-'Wa>00 
WOiOiWOiOiOiOOWtliOOOlOtnOOOiO 

Oi00H*»«4OC0CfiCCi-i*.cstOMit'-JOUOi»4O 
OOOOOOOOiOiOOOKnOtnOOOiOOi 

CnOlOtCnOiOlCnOOC^OiOQOtOOiOiOOiO 

ooh^^iowoj(»hi^-jok)oi-jomoioooi(i 

OOOOOOOCHOiOOOiOlOOlOiOOiOOi 

<ON)OiOOl-'*»-<IOCOO<OOi->£.CncObO>**--ItOlOO} 
O'OiOiOlCflCflO'OOOtaiOOCnOOO'OOiO 

*-*»^]OC005tOt-J£-<IOC0O'00l-'WCi00l-'t£-00 
OOOOOOOOiOiOiOOtnOOOiOOiCliO 


■    ■    -   -         -   j  00  00  00  3 
iococos 


lOWUiOOiOlOOi! 


05w^hP>if.i^oiCiioioooo><i^-jNioooooo-q 

OOOOOOOCBtntnOOOiOOOlOOOiOM 

ccco>^>^-rf^oiCnoioio>Oi02^i-j<i-aoooooooooi 

OiOOh-rf*-»JOWOitOtO^~JOWOiOOOCOC500^ 
OiOiOiOiCntnOiOOOOlOiOOQiOOiOiOOl 

WifM^t^.rf*.mcjiena3C5C3a20^J~-!^ioooooocooi 

OOOOOOOOiOitnOOtnOiOOiOiOWO 

W*.i£.rf».enOiCJiWC»CaC5<IM-J^1000000Oi(Oei 
00^*.^OUO)!OK)Oi-10C<50CIOl-'i^01tDl-'00 

O'Oioioioioi^oiooo'ytoou'OOoiooi 


O&)0)tD100i00fW0>tDKl*-^OC0Oi00OMO 
OOOOOOOOOieiOOtnOOOUOCKCn 

^-^rf^UitnCnCnOsaiCi^-J^J^IOOGOCOOOCOcDOS 
l-'lf^^lOC005tDtN5  0>a>OC001C0>-'l^.<l^!t>30lt0 
CncnOlOiGtOiOiOiOOCTtdOiOCnOiOCnUi© 

^it^>*-aioiOTOcia2cn~4^]<iooooooootD'Xia303 

W02COK>0l00h-l*-O;0t00l00OC0a}00>->>t^OT>*» 
OOOOOOOOOiOiOlOOOiOOtnOOOi 


^^OMOlffltOCnOOH^OltOlOOi-JOMOiOOO 
O>OiOlOiOiOiCnOiOOOOiOiOOOiOOt0O 

i**-#-o<o»cic}OCicn~j<iMoooooooocoto<r>cooi 
Ocotomoc^^^iotooiOoi-'CocicDi-'ii^-iicoo 

OOOOOOOOOitnOiOOtnCnOOiCnOOi 

rf^CnCTO»Cn00505<J^I^3MOOOOOOCOcOCOcDO"^ 
CnCnOiO'OiUiOiCiiUiOOCFiO'OOU'OiOOiO 


^oioioioiQo^i^Js^iooaijoccootoooS 

-    DtOCn^JOCog 

»COOiOOS 


CDtOOlCOH-rfi^lOCOOlOOl- 


OOOOOOOOOOltSt 


> 

cd 
F 

o 


3 

o 

S3 

I— I 

H 

o 

Q 

si 

o 

F 
Q 

a 

F 
te- 
ns 

1— I 

o 
2; 


260      SEROLOGY    OF    NERVOUS   AND    MENTAL  DISEASES 

In  the  determination  of  the  quantity  of  nitrogen  gas  the 
temperature  and  barometric  pressure  must  be  taken  into  con- 
sideration, and  for  this  purpose  the  table  of  Gattermann,  on 
p.  259,  is  utilized.  The  figures  in  that  table  represent  the 
weight  of  amino-nitrogen  in  milligrams,  which  corresponds 
to  1  cm.  of  nitrogen  gas  as  obtained  by  the  action  of  nitrous 
acid,  and  measuring  the  gas  over  water  at  the  given  tem- 
perature and  pressure.  As  the  result  obtained  is  that  for 
moist  nitrogen,  the  figures  obtained  must  consequently  be 
divided  by  two. 

From  an  analysis  of  over  1000  sera  from  various  clinical 
conditions,  the  author  reached  the  conclusion  that  when  the 
amino-content  in  100  c.c.  of  serum  is  2.8  milligrams  or  more, 
it  is  then  to  be  regarded  as  normal;  when  it  is  more  than  2.3 
and  less  than  2.8,  it  is  to  be  considered  as  doubtful,  and  any 
amount  less  than  2.3  milligrams  is  to  be  regarded  as  sug- 
gestive of  syphilis. 

This  reaction  was  not  devised  as  an  additional  test  for 
syphilis,  but  was  established  as  a  means  of  weeding  out 
occasional  conflicting  positive  Wassermann  reactions  ob- 
tained in  patients  who  denied  and  who  did  not  present  any 
clinical  evidence  of  the  existence  of  syphilis. 

In  giving  the  results  obtained  with  this  quantitative  chem- 
ical method,  the  findings  obtained  in  the  third  communica- 
tion, together  with  Dr.  J.  E.  McClelland,  will  be  tabulated, 
N.  Y.  Med.  Jour.,  Nov.  22,  1913.  The  material  was  divided 
into  six  groups: 

Group  1 :    Patients  who  did  not  present  clinical  evidence  of 

syphilis,  who  were  not  treated,  and  who  gave  a 

negative  Wassermann  in  the  serum — in  all,  117 

cases. 

Amino-nitrogen  diminished  in  20  cases,  or  17.6  per  cent. 

Amino-nitrogen  normal        in  94  cases,  or  80.3  per  cent. 

Amino-nitrogen  doubtful      in    3  cases,  or    2.1  per  cent. 

Group  2 :    Patients  who  showed  no  clinical  evidence  of  lues 

were  not  treated,  and  gave  a  positive  Wa'sser- 

mann  in  the  serum — 12  cases. 

Amino-nitrogen  diminished  in    3  cases,  or  25.0  per  cent. 

Amino-nitrogen  normal        in    9  cases,  or  75.0  per  cent. 


THE    AMINO-NITROGEN    CONTENT   OF   SERA  261 

Group  3:  Lues  clinically  present;  patients  were  not  treated 
and  gave  a  positive  Wassermann  in  the  serum — 
40  cases. 

Amino-nitrogen  diminished  in  36  cases,  or  90.0  per  cent. 

Amino-nitrogen  normal        in    3  cases,  or    7.5  per  cent. 

Amino-nitrogen  doubtful      in    1  case,    or    2.5  per  cent. 

Group  4:    Lues  clinically  present;  patients  were  not  treated 

recently,  and  showed  a  negative  Wassermann 

serum — 32  cases.  % 

Amino-nitrogen  diminished  in  26  cases,  or  77.0  per  cent. 

Amino-nitrogen  normal  in  6  cases,  or  23.0  per  cent. 
Group  5 :  Lues  clinically  present,  treated,  showed  a  positive 
serum  Wassermann — 7  cases. 

Amino-nitrogen  diminished  in  3  cases,  or  42.87  per  cent. 

Amino-nitrogen  normal        in  2  cases,  or  28.65  per  cent. 

Amino-nitrogen  doubtful  in  2  cases,  or  28.65  per  cent. 
Group  6:  Lues  clinically  present,  treated,  Wassermann 
reaction  in  serum  negative — 21  cases. 

Amino-nitrogen  diminished  in    8  cases,  or  38.0  per  cent. 

Amino-nitrogen  normal        in  13  cases,  or  62.0  per  cent. 

From  the  foregoing  exposition  it  is  clearly  evident  that  a 
positive  Wassermann  reaction  in  a  patient  exhibiting  no 
clinical  evidence  of  lues  can  be  checked  if  an  estimation  of 
the  amount  of  amino-nitrogen  in  the  patient's  serum  is 
made.  This  is  shown  by  the  results  obtained  in  Group  2. 
It  may  be  stated  that  such  occurrences  are  very  few,  and, 
as  a  rule,  a  positive  serum  Wassermann  when  present  means 
lues;  it  cannot  be  denied,  nevertheless,  that  a  certain  percent- 
age of  errors,  as  in  Group  2,  cannot  be  entirely  avoided.  The 
author  would  suggest,  therefore,  the  adoption  of  the  foregoing 
chemical  analysis  for  the  entire  weeding-out  of  unexpected 
positive  serum  Wassermann  reactions. 

The  Amino-nitrogen  Content  of  Luetic  Sera. — The  vast 
majority  of  syphilitic  material  that  came  under  the  ob- 
servation of  the  author  showed  a  diminished  amount  of 
amino-nitrogen.  This  is,  perhaps,  dependent  upon  a  hy- 
pothesis, suggested  elsewhere,  that  in  order  to  live  and 
propagate,  the  treponema  requires  a  certain  amount  of  this 


262      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

nitrogen  as  food.  The  NH2  side-chain  in  the  serum  molecule 
is  taken  up  in  a  manner  similar  to  that  by  which  the  NH2  is 
probably  anchored  from  the  salvarsan  or  neosalvarsan,  and 
when  one  stops  to  consider  the  structure  of  these  amino-acids 
and  the  drugs  used  to  introduce  arsenic  into  the  economy 
of  the  treponema,  one  can  readily  observe  the  similarity  of 
structure.  The  NH2  molecule  in  both  is  a  side-chain,  and 
not  an  essential  part  of  the  real  nucleus  of  the  substance. 

The  amino-nitrogen  of  syphilitic  sera  is  diminished  in  over 
90  per  cent,  of  untreated  syphilitic  patients,  and  as  the 
system  is  more  or  less  freed  from  the  treponema  there  is  a 
tendency  for  the  amino-nitrogen  to  increase  in  amount.  If  a 
given  serum  does  not  show  a  normal  content  of  amino-nitro- 
gen, regardless  of  the  negative  serum  Wassermann,  it  may  be 
taken  as  a  sign  that  the  microorganisms  are  still  present  in 
large  numbers.  It  must  also  be  remembered  that  this  reac- 
tion has  nothing  in  common  with  the  Wassermann  test,  the 
latter  being  purely  biologic,  whereas  the  former  is  a  chemical 
test,  easily  controllable,  and  having  a  definite  chemical  basis. 

The  Amino-nitrogen  Content  of  Non-luetic  Sera. — From  a 
review  of  the  entire  material  on  the  subject,  it  became  ap- 
parent that  only  7  per  cent,  of  the  clinical  and  biologic  non- 
luetic  cases  gave  a  diminished  amino-content  in  the  serum. 
Regardless  of  the  negative  history  and  absence  of  signs,  a 
number  of  cases  that  showed  diminished  amino-nitrogen 
subsequently  returned  with  unmistakable  symptoms  of 
syphilis.  Among  the  1142  sera  analyzed,  12  gave  a  positive 
Wassermann  in  the  absence  of  clinical  evidence  of  syphilis. 
Of  these  12,  3  showed  a  diminished  amino-nitrogen  content, 
and  of  these  3  patients,  2  returned  with  luetic  skin  lesions. 
The  positive  Wassermann  error  is  reduced  to  less  than  1 
per  cent.,  which  is  the  degree  of  inaccuracy  secured  in  the 
author's  hands  for  the  year  1912-13.  The  last  seven  months 
of  1913  gave  a  percentage  of  error  estimated  at  0.5  per  cent. 
With  amino-control  this  error  was  reduced  to  0.1  per  cent. 

Further  studies  with  this  reaction  are  being  made,  and 
will  cover  a  larger  range  of  clinical  entities,  the  material  here 
considered  having  been  gathered  largely  from  neurologic 
cases,  as  the  original  communications  will  show. 


general  conclusions  263 

General  Conclusions 

The  technology  of  the  subject  of  nervous  and  mental 
diseases  as  here  discussed  includes  the  methods  pursued  by 
the  author  and  those  that  have  proved  of  distinct  value  in 
the  progress  of  this  subject. 

The  serology  of  the  negative  types  (non-luetic  diseases) 
is  very  instructive,  showing  that  a  pleocytosis  may  occur 
even  without  syphilis,  and  helping  to  differentiate  those 
that  are  caused  by  syphilis.  The  most  benefit  will  be  gained 
from  a  study  of  the  serology  of  the  syphilogenous  diseases 
of  the  nervous  system,  where  diagnostic,  therapeutic,  and 
prognostic  information  may  be  secured. 

The  section  on  Salvarsan  is  a  practical  exposition  of  the 
subject,  giving,  besides  the  ordinary  methods  as  gathered 
from  the  literature,  also  such  new  methods  as  have  proved 
of  utility  in  the  treatment  of  nervous  diseases  due  to  syph- 
ilis. It  may  be  repeated  here  that  the  treatment  of  syphilitic 
nervous  diseases  by  salvarsan  and  neosalvarsan  is  still  in 
the  experimental  stage.  We  are  advancing  gradually  to 
that  stage  of  therapy  where  a  retrospect  will  show  how 
far  we  are  from  possessing  a  therapia  sterilisans  magna. 
To  guarantee  a  cure  to  the  patient  suffering  from  a  syphilitic 
nervous  disease,  and  even  to  state  a  time  when  this  will  be 
accomplished,  will  not  be  the  practice  of  a  conscientious 
physician :  all  that  can  be  accomplished  today  is  to  effect  an 
amelioration  of  the  active  and  painful  manifestations. 
Occasionally  a  fixed  pupil  will  become  mobile  or  the  memory 
defect  may  disappear,  but  no  promise  of  these  things  can 
as  yet  be  held  out  by  physicians  to  their  patients. 

Syphilis  itself  and  its  active  manifestations  will  be  in- 
fluenced by  salvarsan,  but  the  outcome  of  syphilis,  what- 
ever this  may  be,  still  remains  sub  judice.  Our  chief  efforts 
today  are  directed  toward  removing  active  manifestations, 
and  thereby  minimizing  the  formation  of  permanent  tissue 
changes.  These  manifestations  in  syphilitic  diseases  of  the 
nervous  system  can  be  determined  by  proper  serologic  in- 
vestigation. 


LITERATURE 

The  literature  of  salvarsan  and  neosalvarsan  is  so  extensive  that  to 
attempt  to  give  even  a  partial  review  of  the  treatment  of  syphilis  with 
this  remedy  would  require  a  volume  larger  than  the  one  here  offered. 
Very  instructive  reading  is  to  be  had  in  Ehrlich's  Abhandlungen  ueber 
Salvarsan,  3  volumes,  J.  F.  Lehmann,  Munich. 
Benario,  J.:  Ueber  Neurorezidive,  J.  F.  Lehmann,  Munich. 
Ehrlich-Hata:    Die    experimentelle    Chemotherapie    der    Spirillosen, 

Julius  Springer,  Berlin. 
Gennerich,   W. :  Die  Liquorveranderungen  in  den  einzelnen  Stadien 

der  Syphilis,  August  Hirschwald,  publishers,  Berlin,  1913. 
Lenzmann,  R.:  Salvarsan,  Jena,  Gustav  Fischer. 
Milian,  G.:  Traitement  de  la  syphilis,  by  J.  B.  Bailliere  et  fils,  Paris, 

1912. 
Pinkus,  FeUx:  Ueber  den  Stand  unserer  Kenntnisse  vom  Salvarsan, 

Urban  and  Schwarzenberg,  Berlin. 
Schmitt,  A.:  Wirkhche  und  angebhche  Schadigungen  durch  Salvarsan, 

Curt  Kabitzsch,  Wurzburg. 
Stokar,  Kurt  von:  Die  Syphilis-Behandlung  mit  Salvarsan,  Lehmann, 

Munich. 
Tomasczewski,   E.:   Die   Technik  der   Salvarsanbehandlung,   Thieme, 

Leipzig,  1911. 
Wechselmann,  W.: 

Die  Behandlung  der  Syphilis  mit  Dioxydiamidoarsenobenzol,  Oscar 
Coblentz,  Berlin. 

Ueber    die    Pathogenese    der    Salvarsantodesfalle,    Urban    and 
Schwarzenberg,  Berlin. 


ENGLISH  LITERATURE 

Ager:  Urotropin,  Medical  Annual,  p.  503,  1908. 

Allen:  Cholin.  A  New  Method  of  Testing  for  its  Presence  in  the 
Blood  in  Cerebrospinal  Fluid,  Proc.  of  the  Phys.  Soc,  July  29,  1904. 

Allen  and  French:  Some  Observations  Upon  the  Test  for  Cholin  in 
Human  Blood,  Proc.  of  the  Phys.  Soc,  Nov.  14;  Jour,  of  Phys., 
p.  30,  1903. 

Amsden:  Report  of  Certain  Lumbar  Punctures  at  Bloomingdale  Hos- 
pital, N.  Y.  Med.  Jour.,  1910,  438. 

Atwood,  C.  E.:   Idiocy  and  Hereditary  Syphilis,   Jour.  Amer.  Med. 
Assoc,  1910,  p.  464. 
264 


LITERATURE  265 

GERMAN  LITERATURE 

Abraham  and  Ziegenhagen:   Ueber  cytodiagnostische  Untersuchungen 

bei  Dementia  paralytica,  Cent.  f.  Nervenh.  u.  Psy.,  1904,  xxvii,  323. 

Abramof,  S.:  Ueber  den  Einfluss  der  Reaktion  auf  die  Komplement- 

bindungs  phanomene  und  die  sie  vermittelnden  Komponenten, 

Zeitschr.  f.  Immunit.,  1910,  145. 

Alexander,  A. :  Serodiagnostische  Untersuchungen  zur  Frage  der  Bezie- 

hungen  zwischen  Ozsena  und  Syphilis,  Zeitschr.  f.  Laryng.,  1910, 

p.  669. 

Allaria:  Ueber  die  Natur  der  haemolytischen  Erscheinung  der  cerebro- 

spinalfluessigkeit,  Revista  di  Clinica  pediatrica,  No.  6,  1907. 
Alt:  Das  neue  Ehrlich-Hata   Praparat  gegen  syphihs,  Munch,  med. 

Woch.,  1910,  No.  11,  561. 

Alzheimer:  Einige  Methoden  zur  fixierung  der  zelhgen  Elemente  der 

Cerebrospinalflussigkeit,  Centr.  f.  Nervenh.  u.  Psy.,  1907,  No.  239. 

Andernach:    Beitrage   zur   Untersuchung   des   Liquor    cerobrospinalis 

mit  besonderer  Beruecksichtigung  der  zelhgen  Elemente,  Arch.  f. 

Psy.  u.  Nervenheilk.,  47,  2,  1910. 

Angerer,  C:  Ueber  Amboceptorwirkung  in  Salzlosung  verschiedener 

Konzentration,  Zeitschr.  Immunitatsf.,  1910,  p.  243. 
Apel:    Beitrage  zur  Frage   der    Berechtigung  der  spinalen  und  cere- 

bralen  Punktion,  Berl.  klin.  Woch.,  1910,  p.  1540. 
Apelt: 

Die  Bedeutung  cytologischer  Untersuchungen  der  Cerebrospinal- 
fluessigkeit  fuer  die  Neurologie,   Monatschr.  f.  Psy.,   20,  Erg. 
H.  I,  1906. 
Untersuchungsergebnisse  am  Liquor  von  Trypanosomen  infizierten 

Hunden,  Cent.  f.  Nervenh.  u.  Psy.,  1908,  xxxi,  975. 
Untersuchungen  des  Liquor   cerebrospinalis  auf  Vermehrung  der 
zelhgen  Elemente  und  Eiweisskoerper  bei  Trypanosomiasis  der 
Hunde,  Munch,  med.  Woch.,  1909,  No.  44. 
Zum  Wert  der  Phase  I  fuer  die  diagnose  in  der  Neurologie,  Arch, 
f.  Psy.,  46,  1,  1909. 
Apelt  and  Schumm:  Untersuchungen  ueber  Phosphorsauregehalt  der 

Spinalfliissigkeit.,  Arch.  f.  Psy.,  1908,  xliv,  p.  2. 
Arzt  and  Boese:  Ueber  Paratyphus  Meningitis  im  Kindesalter,  Wien. 

klin.  Woch.,  No.  7,  1908. 
Aschenheim,  Erich: 

Ueber  die  naturlichen  haemolytischen  Zwischenkorper  des  mensch- 

lichen  Blutes,  Cent.  f.  Bact.,  1909,  xlix,  I.  Abt.,  Orig.,  124. 
Serumkomplementbestimmung  im  homologem  System,  Centralbl. 
f.  Bakt.,  1909,  p.  424. 
Assman,  H.: 

Diagnostische  Ergebnisse  aus  der  Lumbalpunction  von  150  Faellen 
mit  besonderer  Beruecksichtigung  der  Nonne-Apeltschen  Reac- 
tion, Duet.  Zeits.  f.  Nervenh.,  1910,  xl,  No.  131. 


266      SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

Aasman,  H.:  Erfahrungen  ueber  Salvarsan-Behandlung  luetischer  und 
metaluetischer  Erkrankungen  des  Nervensystems  unter  Contro 
durch  die  Lumbalpunction,  Deut.  med.  Woch.,  1911 

FRENCH  LITERATURE 

Abadie:  Resultats  de  l'examen*cytologique  de  quelques  liquides  cephalo- 

rachidiens,  Compt.  rend,  de  la  Soc.  de  Biol.,  25,  946,  1902. 
Abundo:  Sulle  vie  linfatiche  del  Sistema  nervosa  centrale,  Ann.  di  Neu- 

rologia,  1896. 
Acchiote:    Poliomyelite    anterieure     aigue    et    lymphocytose,    Revue 

Neurol.,  19,  1911. 
Achard: 

Microbes  dans  cellule  dans  le  liquide  de  la  ponction  lombaire,  Soc. 

Med.  des  H6p.,  Nov.  13,  1908. 
Examen  du  liquide  cephalorachidien,  Gaz.  hebd.  de  med.  et  chir., 
July  21,  1901. 
Achard  and  Landry:  Contribution  a  la  cryoscopie  du  liquide  cephalo- 
rachidien, Arch,  de  med.  experim.,  1901,  567. 
Achard  and  Loeper:  Deux  cas  de  fievre  zoster  aved  examen  microbio- 
logique  du  liquide  cephalo-rachidien,  Bull.  Soc.  med.  des  hop., 
July  26,  1901. 
Variations  comparatives  de  la  composition  du  sang  et  des  seros- 
ites,  C.  R.  Soc.  Biologie,  18  juin,  p.  645  et   Presse  Med.,  No. 
73,  1901. 
Passage  du  ferrocyanure  de  potassium  dans  l'humeur  aqueuse  an 
cas  d'obstacle  a  1' elimination  renale,  C.  R.  Soc.  Biol.,  15  M,  1902. 
Allaria: 

Action  du  liquid  cephalo-rachidien  sur  quelques  bacteries,  11  Mor- 

gagni  47,  No.  11,  1905. 
La  reazione  attuale  e  la  reazione  potenziale  del  liquido  cerebro- 
spinale  a  meningi  sane  e  nelle  meningiti,    Archivi  delle  scienze 
medicale,  32,  3,  1908. 
Anfinoff  (1907):  Hemorragies  menues  sur  la  surface  cerebrale  comme 
phenomene  constant  dans  le  l'epilepsie  et  leur  signification,  Revue 
Russe  de  Psychiatrie    de    Neurologie  et  de  Psychologie  experi- 
mentale,  No.  5,  p.  257;  Revue  Neurologique,  1908,  p.  243. 
Anglada: 

Le  liquide  cephalo-rachidien;   bilan  actuel  du  diagnostic  par  la 

ponction  lombaire,  These  de  Montpellier,  1909. 
Le  liquide  cephalo-rachidien;  sur  ces  propriety  physiques,  physio- 
logiques   et  biochemiques,    chemiques,   microbiologiques,    cyto- 
logiques,  Revue  generale  in  Gaz.  des  Hop.,  March  26,  No.  36, 
1910. 
Le  liquide  cephalo-rachidien,  Paris,  1910  (literature). 
Le  liquide  cephalo-rachidien;  sur  ces  proprietes  physiques,  physio- 
logiques   et   biochimeques,   chemiques,   microbiologiques,  cyto- 
logiques,  Gaz.  des  Hop.,  March  26,  1910. 


LITERATURE 


267 


Anglada  and  Jacquin  (1906) :  A  propos  des  quelques  resultas  pratiques 
et  immediates  obtenues  par  la  ponction  lombaire,  Soc.  de  Medi- 
cine et  de  Chirurgie  de  Bordeaux,  April  6th;   Gaz.  hebdom.  des 
Sciences  med.  de  Bordeaux,  No.  25,  June  24th. 
Ardin-Delteil: 

Indications  diagnostiques  fournies  par  la  coloration  du  liquide, 

C.  R.  MontpeUier  Medicale,  16,  p.  25,  1903. 
Le  liquide  cephalo-rachidien  des  Paral.,  Gen.  Rev.  Neurol.,  p.  1212, 

Dec.  3,  1903. 
Le  liquide  cephalo-rachidien  des  paralytiques  genereaux,  Revue 
Neurol.,  Dec,  1903. 
Ardin-Delteil  and  Monfrin  (1903) :  Toxicite  du  liquide  cephalo-rachidien 

des  Paral.,  Gen.  C.  R.  Soc.  Biol.,  November,  p.  1512. 
Armand-Delille : 

Toxicite  du  liquide  ceph.   rach.  et  la  mening.  tubercul.,  C.  R. 

Soc.  Biol.,  p.  1010,  1902. 
Role  des  poison  du  bacille  de  Koch  dans  la  meningite  tubercu- 

leuse,  These  de  Paris,  No.  449,  1903. 
Reaction  de  Wassermann   dans  le  liquide  cephalo-rachidien  des 
paralytiques  genereaux,  Soc.  med.  des  Hop.,  1907,  xxiv,  1570. 
Aubry:  Le  syndrome  de  coagulation  massive  du  liquide,   These  de 
Paris,  1909. 

B 

ENGLISH  LITERATURE 

Bailey: 

Cryoscopy  of  the  Cerebrospinal  Fluid  in  Epidemic  Cerebrospinal 

Meningitis,  N.  Y.  Medical  Record,  No.  6,  1905. 
The  Serum  Diagnosis  of  Syphilis;  an  Analysis  of  Two  Hundred 
Consecutive  Sera  Examined  for  the  Wassermann  Reaction  in 
which  a  Modified  Neisser  Technic  was  Used,  Lancet,  p.  1523, 
1909. 
Ball,  C.  R.:  The  Value  of  the  Four  Reactions  in  the  Diagnosis  and 
Treatment  of  Syphilitic  Diseases  of  the  Nervous  System,  Jour. 
Amer.  Med.  Assoc,  Oct.  5,  1912. 
Battersby  :  Congenital    and  Acquired  Hydrocephalus,   Medical    and 

Surgical  Journal,  Edinb.,  July,  1850. 
Bolduan: 

Immune  Sera,  John  Wiley  &  Sons,  N.  Y.,  1908. 
Collected  Studies  on  Immunity,  by  Prof.  Paul  Ehrlich,  John  Wiley 
&  Sons,  N.  Y.,  1908. 
Boyd:   Cerebrospinal   Fluid  in  Mental  Conditions,  Jour,  of   Mental 

Sciences,  1912,  58. 
Browning  and  McKenzie: 

Modifications  of  Serum  and  Organ  Extract  Due  to  Physical 
Agencies,  and  their  Effect  on  the  Wassermann  Syphilis  Reac- 
tion, Jour,  of  Path,  and  Bact.,  1909,  xiii,  325. 


268      SEROLOGY   OF   NERVOUS    AND   MENTAL   DISEASES 

Browning  and  McKenzie: 

The  Biological  Syphilis  Reaction,  its  Significance  and  Method  of 

Application,  Lancet,  1909,  i,  1521. 
On  the  Wassermann  Reaction  and  Especially  its  Significance  in 

Reaction  to  General  Paresis,  Jour,  of  Mental  Science,  1909. 
On  the  Complement  Containing  Serum  as  a  Variable  Factor  in 
the  Wassermann  Reaction,   Z.   f.   Immunitaetsforsch,    1909,  i, 
459. 
Bury  and  Ransbottom:  On  Lymphocytosis  of  the  Cerebrospinal  Fluid 

in  Relation  to  Tabes,  The  Quarterly  of  Medicine,  Oct.  9,  1909. 
Butler:  Serum  Diagnosis  of  Syphilis,  Jour.  Amer.  Med.  Assoc,  1908, 
li,  824. 

GERMAN  LITERATURE 

Bab:  Kurze  Mittheilung  zu  dem  Aufsatz  von  Wassermann  und  Plant 
ueber  syphilitische  Antistoffe  in  der  Cerebrospinalfluessigkeit 
von  Paralytikern,  Deut.  med.  Woch.,  1906,  1895. 

Baetzner:  Die  Bedeutung  der  Wassermannschen  Reaction  fuer  die 
Differentialdiagnose  der  chirurgischen  Syphilis,  Munch,  med. 
Woch.,  1909,  330. 

Baginsky,  A.:  Pathologie  der  Parasyphilis  im  Kindesalter,  Arch.  f. 
Kinderheilk.,  1910,  p.  133. 

Baisch:  Die  Vererbung  der  Syphilis  auf  Grund  serelogischer  und  bakte- 
riologischer  Untersuchungen,  Munch,  med.  Woch.,  1909,  p.  1920. 

Ballner  and  Decastello :  Ueber  die  klinische  Verwertbarkeit  der  komple- 
mentbindungsreaction  fuer  die  Serodiagnostic  der  Syphilis,  Deut. 
med.  Woch.,  1908,  xxxiv,  1923. 

Balogh:  Beitrage  zur  Bestimmung  des  Cytodiagnostischen  Wertes  der 
Liquor  cerebrospinalis,  Orvosi  Hetelap,  8,  1905. 

Bang,  Ivar:  Biochemie  der  Zelhpoide,  II,  Asher  Spiro's  Ergebnisse  der 
Physiologie,  1909,  viii,  466-517. 

Baron:  Das  Eiweisgehalt  und  die  Lymphocytose  der  Liquor  cerebro- 
spinalis bei  Saeuglingen  mit  Lues  congenita,  Jahrbuch  f.  Kinder- 
heilkunde,  1909,  69,  i. 

Bauer,  J. : 

Zur  Methodik  des  serologischen  Luesnachweises,  Duet.  med.  Woch., 

1908,  698. 
Wassermannsche  Luesreaction,  Berl.  klin.  Woch.,  1908,  834. 
Ueber  die  Wassermannsche  Luesreaction  wirksamen  Koerper,  und 
ueber  die  haemolytischen  Eigenschaften  der  Organextracte,  Bio- 
chemische  Zeitschr.,  1908,  x,  304. 
Das  Colle'sche  und  Profeta'sche  Gesetz  im  Lichte  der  modernen 
Serumforschung,  Wien.  klin.  Woch.,  1908,  xxi,  1259. 

Bauer,  R.,  and  Hirsch,  A.:  Beitrage  zum  Wesen  der  W.  R.,  Wien.  klin. 
Woch.,  1910,  xxiii. 

Bauer  and  Meyer:  Zur  Technick  und  klinischen  Bedeutung  der  Wasser- 
mannschen Reaction,  Wiener  klin.  Woch.,  1908,  No.  51. 


LITERATURE  269 

Beck,  K. :  Ueber  die  Verwendbarkeit  der  W.  R.  in  der  Otiatrie,  Zeitschr. 

f.  Ohrenheilk.,  1910,  218. 

Beckers:  Zur  Serodiagnostik  der  Syphilis,  Munch,  med.  Woch.,  1909,  551. 

Beltz:  Ueber  Liquoruntersuchungen  mit  besonderer  Beruecksichtigung 

der  Nonne-Apelt'schen  Reaction,  Deut.  Zeitschr.  f.  Nervenheilk., 

1911,  43,  1  and  2. 

Bendixson:    Psychiatrische    Erfahrungen    mit  der   Wassermannschen 

Reaction,  Zeitschr.  f.  Immunitatsf.,  vol.  iv,  No  .3,  pp.  349-356. 
Beneke:  Die  Wassermannsche  Syphilis  Reaction,  Berl.  klin.  Woch., 

1908,  730. 
Berdach:  Bericht  ueber  die  Meningitis  Epidemie  in  Trifail  im  Jahre 

1898,  Arch.  f.  klin.  Med.,  65,  449,  1900. 
Bergl  and  Klausner:  Ueber  das  Verhalten  des  Liquor  cerebrospinalis 

bei  Luetikern,  Prager  med.  Woch.,  37,  1912. 
Bering,  Fr. : 

Die  praktische  Bedeutung  der  Serodiagnostik  bei  Lues,  Munch. 

med.  Woch.,  1908,  2476. 
Was   leistet  die  Seroreaction  fuer  die   Diagnose,  Prognose,  und 

Therapie  der  Syphilis,  Arch.  f.  Dermat.  u.  Syph.,  1909,  p.  301 
Welche   Aufschluesse  liefert  die  Seroreaktion   ueber  das  Colles- 
Baumesche  und  das  Profetasche  Gesetz,   Deut.  med.  Woch., 
1910,  219. 
Berneheim  and  Moser:  Ueber  diagnostische  Bedeutung  der  Lumbal- 

punction,  Wiener  klin.  Woch.,  1897,  20  and  21. 
Bertels  and  Schwarz:  Ueber  "Meningitis"  carcinomatosa,  Deut.  Zeit. 

f.  Nervenh.,  1911,  42. 

Bertelsen  and  Bisgaard:  Resultate  objectiver  Ausmessung  der  biolo- 

gischen,  cytologischen  und  chemischen  Reactionen  in  der  Cere- 

brospinalfluessigkeit,  besonders  bei  Paralytikern,  sowie  Beschrei- 

bung  einer  neuen  chemischen  Reaction  in  der  Spinalfluessigkeit, 

Zeitschrift  f.  d.  ges.  Neur.  u.  Psych.,  1911,  4. 

Biach,  M.:  Psoriasis  vulgaris  und  W.  R.,  Wien.  med.  Woch.,  1910,  No.  20. 

Binswanger  and  Berger:  Beitrage  zur  Kenntniss  der  Lymphzirculation 

in  der  Grosshirnrinde,  Virchow's  Arch.,  1898,  152. 
Bisgaard : 

Zur  Differentialdiagnose  zwischen  Dementia  Paralytika  und  Lues 
des  zentralnervensystems,  Arch.  f.  d.  ges.  Neurol,  and  Psych., 
1912,  381. 
Ueber  ein  regelmaessiges  Verhaeltniss  zwischen  Eiweis  und  Was- 
sermann  Reaction  in  der  Cerebrospinalfluessigkeit  der  Para- 
lytiker,  Zeitschrift.  f.  die  gesammte  Neurol,  and  Psych.,  1912, 
10,  4  and  5,  660. 
Bizzozero,  Enzo:  Ueber  den  Einfluss  der  Jodkali  Behandlung  auf  die 

W.  R.,  Med.  Klin.,  1901,  No.  31. 
Blaschko : 

Die  Bedeutung  der  Serodiagnostik  fuer  die  Pathologie  und  Ther- 
apie der  Syphilis,  Berl.  klin.  Woch.,  1908,  694. 


270      SEROLOGY  OF   NERVOUS   AND   MENTAL   DISEASES 

Blaschko:   Ueber   die    klinische    Verwertung    der   Wassermannschen 

Reaction,  Deut.  med.  Woch.,  1909,  xxxv,  383. 
Blumenthal: 

Serodiagnose  der  Syphilis,  Dermat.  Zeits.,  1910,  vol.  xvii. 

Ueber  Cerebrospinalfluessigkeit,  Ergebnisse  der  Phys.,  1902,  i. 
Blumenthal  and  Roscher:  Die  Bedeutung  der  Wassermannschen  Reac- 
tion bei  der  Syphilis,   wehrend  ersten,   der  Infection  folgenden 

Jahre,  Med.  Klin.,  1909,  241. 
Blumenthal  and  Wile:  Ueber  Komplementbindende  Stoffe  im  Harn 

Syphilitischer,  Berl.  khn.  Woch.,  1908,  1050. 
Boas,  Harold: 

Die  Wassermannsche  Reaction  mit  besonderer  Beruecksichtigung 
ihrer  khnischen  Verwertbarkeit,  Karger,  Berlin,  1911. 

Die  Bedeutung  der  Wassermannschen  Reaction  fuer  die  Therapie 
der  Syphilis,  Berl.  khn.  Woch.,  1909,  588. 

Die  W.  R.  bei  aktiven  und  inaktiven  Sera.,  Ibid.,  1909,  p.  400. 

Die  W.  R.,  Berlin,  S.  Karger,  1911. 
Boas  and  Hauge:  Komplementablenkung  bei  Scharlach,  Berl.  klin. 

Woch.,  1908,  1566. 
Boas  and  Lind:  Untersuchungen  der  Spinalfluessigkeit  bei  Syphilis 

ohne  Nervensymptome,  Zeits.  f.  d.  ges.  Neur.  und  Psych.,  1911, 

Orig.  4,  689. 
Boas  and  Neve: 

Die  W.  R.  bei  Dementia  paralytika,  Berlin,  klin.  Woch.,  1910, 
p.  1368. 

Untersuchungen  ueber  die  Weil-Kafkasche  Haemolysin-Reaction 
in   der  Spinalfluessigkeit,  Zeit.  f.  d.  Neur.  and  Psych.,  1912, 
4  and  5. 
Boehm:    Malaria   and   Wassermann    Reaction,   Arch.  f.  Schiffs    und 

Tropenhyg.,  1909,  xiii,  Beiheft  6. 
Bonfiglio:   Die  Wassermannsche  Reaction  bei   Geistes  und   Nerven- 

krankheiten,  insbesondere  bei  Tabes  Dorsalis,  Lecture  at  the  Psy- 
chiatric Congress  in  Perugia,  1911. 
Bonhoeffer:  Bemerkungen   zur   Behandlung  und   Diagnose  der  Pro- 

gressiven  Paralyse,  Berl.  khn.  Woch.,  1910,  47. 
Bonhoff:  Ueber  das  Vorkommen  von  virulenten  Diphtherie  Bacillen 

im   Blute   und   in   der   Cerebrospinalfluessigkeit   des   Menschen, 

Zeitschrift  f.  Hygiene,  1910,  67. 
Brauer:  In  welcher  Weise  wirkt  das  Hg.  bei  der  antiluetischen  Behand- 
lung   auf  den  Ausfall    der    Seroreaktion,   Munch,   med.   Woch., 

1910,  905. 
Braun:  Ueber  die  Lumbalpunction  und  ihre  Bedeutung  fuer  die  Chi- 

rurgie,  Arch.  f.  klin.  Chir.,  1897,  54. 
Braun,  A. :  Ueber  den  Nachweis  der  Antigene  mittels  der  komplement- 

fixationsmethode,  Berl.  khn.  Woch.,  1907,  1535. 
Braun  and  Husler:  Eine  Neue  Methode  zur  Untersuchung  der  Lumbal- 

punctate,  Deut.  med.  Woch.,  1912,  3825. 


LITERATURE  271 

Browning,  Cruikshank,  and  Mackenzie:  Gewebskomponenten,  die  bei 
der  W.  R.  beteiligt  sind,  insbesondere  Lecithin  mid  Cholesterin, 
Biochem.  Zeitschr.,  1910,  85. 
Brack,  C  : 

Die  Sere-diagnose  der  Syphilis,  Springer,  Berlin,  1909. 

Zur  forensischen  Verwertbarkeit  und  Kenntniss  des  Wesens  der 

Komplementbindung.,  Berl.  klin.  Woch.,  1907,  1510. 
Ueber    die    klinische  Verwertbarkeit    der    Komplementbindungs- 
reaction  fuer  die  Serodiagnostic  der  Syphilis.,  Deut.  med.  Woch., 
1908,  2178. 
Zur  biologischen  diagnose  von  Infectionskrankheiten,  Deut.  med. 

Woch.,  1906. 
Ueber  das  angebliche  Vorkommen  der  Syphilisreaktion  bei  Psori- 
asis vulgaris,  Wien.  klin.  Woch.,  1910,  704. 
Ueber  das  angebliche,  etc.  (same  title  as  above),  Bemerkungen  zu 
der  Arbeit  von  G.  Gjorgjevic  und  Paul  Savnik.,  Wien.  klin. 
Woch.,  1910,  778. 
Brack  and  Cohn:  Scharlach  und  Serumreaktion  auf  Syphilis,  Berl. 

klin.  Woch.,  1908,  2268. 
Brack  and  Gessner:  Ueber  Serum  Untersuchung  bei  Lepra,  Berl.  klin. 

Woch.,  1909,  589. 
Bruck  and  Stern: 

Die  Wassermann-Neisser-Brucksche  Reaction  bei  Syphilis,  Deut. 

med.  Woch.,  1908,  401,  459,  504. 
Hg.  Wirkung  und  Syphilisreaktion,  Wien.  klin.  Woch.,  1910,  534. 
Ueber  das  Wesen  der  Syphilisreaktion,  Zeitschr.  f.  Immunitatsf., 
1910,  592. 
Brueckner:  Ueber  die  Beziehungen  der  Syphilis  zur  Idiotie,  Munch. 

med.  Woch.,  1910,  37. 
Bruhns  and  Halberstaedter:  Zur  praktischen  Bedeutung  der   Serodi- 

agnostik  der  Syphilis,  Berl.  klin.  Woch.,  1909,  149. 
Buschke:  Diagnose  und  Therapie  der  Syphilis,  auf  Grand  der  neueren 

Forschungsergebnisse,  Berl.  klin.  Woch.,  1910,  869. 
Buschke  and  Harder:  Ueber  die  Provokatorische  Wirkung  von  Sublimat 
Injektionen  und  deren  Beziehungen  zur  W.  R.  bei  Syphilis,  Duet, 
med.  Woch.,  1909,  1139. 

FRENCH  LITERATURE 

Babinski:  Meningite  hemorragique  fibrineuse.  Parapl6gie  spasmodique 

lombaire.   Traitement  mercuriel.   Guerison,   Soc.   med.   d.   Hop., 

Oct.  23,  1903. 
Babinski  and  Nageotte:  Contribution  a  l'etude  du  cytodiagnostic  du 

liquid  cephalorachidien  dans  les  affections  nerveuses,  Bull.  Soc. 

med.  des  Hop.,  1901,  18. 
Backman  and  Jacobaeus:  Sur  la  quantite  de  complement  et  d'ambocep- 

teur  et  la  qualite  hemolytique  du  serum  humain  physiologique,  C. 

R.  Soc.  Biol.,  1909,  415. 


272      SEROLOGY  OF   NERVOUS    AND    MENTAL   DISEASES 

Banque:  Reaction  du  liquide  C.  R.  au  cours  de  la  Pachymeningite 

pottique,  These  de  Paris,  July  12,  1911. 
Bar  and  Daunay:  Valeur  de  la  reaction  de  Wassermann  au  point  de 

vue  du  diagnostic  de  la  syphilis  latente  chez  le  neuveau-ne,  C.  R. 

Soc.  Biol.,  1908,  1085. 
Bard: 

Methode  de  determination  de  la  tonicite  du  liquide  C.  R.  par  son 
action  sur  le  globules  rouge  du  porteur,  C.  R.  Soc.  Biol.,  Feb. 
16,  1901. 

Procede  clinique  de  determination  de  Tisotonicite  du  liquide 
cephalo  rachidien,  Bull.  Med.,  Jan.  5,  1901. 

Du  variations  pathologiques  du  pouvoir  hemolytique  du  Uquide 
cephalo-rachidien,  La  Semaine  med.,  Jan.  13,  1903. 

Des  colorations  du  liquide  C.  R.  d'origine  hemorragique,  Semaine 
med.,  Oct.  14,  1903. 

De  la  coloration  biliare  du  Uquide  C.  R.  d'origine  hemorragique, 
C.  R.  Soc.  Biologie,  Nov.  28,  1903. 
Barie   and  Lian:    Convulsions  epileptiformes  et  hemiplegie  au  coura 

d'une  fievre  typhoide,  Soc.  med.  d.  Hop.,  Oct.  25,  1907. 
Barthe:  Analyse  d'un  hquide  cephalo  rachidien,  Bull,  des  travaux  de 

la  Soc.  de  Pharmacie  de  Bordeaux,  1898,  p.  246. 
Baudoin  and  Franf  ais :  La  reaction  butyrique  de  Noguchi  et  Moore  dans 

le  Diagnostic  des  Affections  Syphulitiques   du  Nevraxe,  Revue 

Neurologique,  May  1910,  p.  620. 
Bauer   and  Maubah:   Me'ningite,   cerebro-spinale  hemorragique  aigue 

Archives  generates  de  Medicine,  Nov.  3,  1903. 
Beaussart:  Etude  du  hquide  C.  R.  des  Syphulitiques  et  Parasyphili- 

tiques:   Cyto-diagnostic,   Albumo-diagnostic,  Precipito-diagnostic, 

Reaction  butyrique  de  Noguchi  et  Moore,  La  Clinique,  January, 

27,  1911. 
Beletre:  La  ponction  lombaire  chez  les  syphilis,  These  de  Paris,  1912. 
Belletrud:    Etude   bacteriologique  "postmortem"  du  hquide  cephalo- 
rachidien  des  alienes,  Revue  de  Psych.,  1908. 
Belliisari:    Toxicite    du    hquide    cephalo-rachidien    dans   la   paralysie 

generale,  Riv.  med.,  1899. 
Bernard  and  Troisier:  Sur  un  cas  d'intoxication  saturnine  avec  Menin- 

gite  ancienne  et  Ictere,  Soc.  med.  d.  Hop.,  May  22,  1908. 
Beryon  and  Cade:  Liquide  cephalo-rachidien  et  meningite  dans  un  cas 

de  maladie  de  Friedreich,   C.   R.   de  la  Soc.   de  Biol.,   1901,  p. 

247. 
Bierry  and  Lalou:  Variations  du  Glucose  du  Sang  et  du  hquide  cephalo- 
rachidien,  C.  R.  Soc.  Biol.,  February  13,  1904. 
Blanchetiere  and  Lejonne: 

Syndrome  de  coagulation  massive  et  de  xanthochromic  du  hquide 
C.  R.  sans  elements  cellulaires,  dans  un  cas  de  Sarcome  de  la 
dure-mere,  C.  R.  Soc.  Biol.,  May  15,  1909,  and  Gazette  des 
Hopitaux,  Sept.  14,  No.  104. 


LITERATURE  273 

Blum :  Acetone  et  corps  acetoniques  rachidiens  dans  le  coma  diabetique, 

Congres  Frangais  de  medicine,  Lyons,  1911,  p.  70. 
Boidin  and  Weil:  Meningite  syphilitique  secondaire  aigue,  Presse  med., 

1907,  p.  661. 
Bonnotte:  Contribution  a  l'etude  des  variations  du  taux  de  l'uree  dans 

le  liquide  C.  R.  a  l'etat  pathologique  et  principalement  au  cours 

de  l'uremie,  These  de  Lyons,  Dec.  16,  1909,  No.  23. 
Bordet: 

La  methode  de  mise  en  evidence  des  sensibilisatrices  et  ses  appli- 
cations recentes,  Bull,  de  l'Academie  Royale  de  Belgique,  1906, 
xx,  454. 

La  fixation  de  l'alexine  et  sa  signification  pour  l'immunite,  Z.  f. 
Immunitatsforschung,  1909. 
Bordet  and  Gay :  Sur  les  relations  des  sensibilisatrices  avec  l'alexine, 

Ann.  Inst.  Pasteur,  1906,  xx,  467. 
Bordet  and  Gengou:  Sur  1' existence  des  substances  sensibilisatrices 

dans   la   plupart  de  serums    antimicrobiens,  Ann.  Inst.  Pasteur, 

1901,  289. 
Bougault:  Sur  la  reaction  de  Florence,  Jour.  d.  Pharm.  et  de  Chim., 

1909,  p.  185. 
Bousquet:  Le   Meningisme,   ses  raports  avec  la  ponction  lombaire, 

Gazette  des  Hop.,  June  23,  1910. 
Bousquet  and  Derrien: 

Sur  la  presence  de  composes  acetoniques  dans  le  liquide  cephalo- 
rachidien  au  cours  du  diabete  et  en  dehors  du  coma,  Mont- 
pellier  Medical,  1908,  p.  183. 

Acetonemie  et  acetone  dans  liquide  cephalo-rachidien,  C.  R.  de 
la  Soc.  Biol.,  1910,  1002. 
Boveri: 

Tension  du  liquide  C.  R.,  C.  R.  Soc.  Biol.,  May  20,  1911. 

Le  liquide  C.  R.  dans  la  Pellagre,  C.  R.  Soc.  Biol.,  June,  10,  1911. 
Braillon:  Hemorragie  sous-arachnoidienne  curable,  Gaz.  d.  Hop.,  1909, 

p.  635. 
Brandeis  and  Mongour:  Valeur  comparee  de  l'albumo-diagnostic  et  du 

cy to-diagnostic  du  liquide  C.  R.,  Communication  a  la  Societe  de 

Med.  et  de  Chirurgie  de  Bordeaux,  April  22,  1906. 
Breton:  Cyto-diagnostic,  Gazette  des  Hop.,  1901,  p.  949,  vol.  Ixxiv. 
Brissaud  and  Sicard:  Cytologie  du  liquide  C.  R.  au  cours  du  zona  thor- 

acique,  Soc.  med.  d.  Hop.,  March  15,  1901. 
Broden  and  Rodhain:  Le  liquide  c6phalo-rachidien  dans  la  trypanoso- 

miase  humaine  (maladie  de  sommeil),  La  Nevraxe,  1909. 
Bruckner  and  Galasesco:  Syphilis  et  insufficiance  aortique,  C.  R.  Soc. 

Biol.,  1910,  74. 
Bruneau:  De  la  valeur  de  la  ponction  lombaire  pour  le  diagnostic  de 

Themorragie  m6ning6e,  Marseille  Medical,  April  1,  1902. 


18 


274      SEROLOGY   OF   NERVOUS   AND    MENTAL   DISEASES 

ITALIAN  LITERATURE 

Bergamesco:  Sul  liquido  cerebrospinale,   Riv.   crit.   di   clinica  med., 

1908,  36,  9. 
Borrelli  and  Datta:  Viscosimetria  del  liquido  cerebrospinale,  La  clinica 

med.  ital.,  1906,  45. 
Borrelli  and  Messineo:  DelT influenza  della  cura  arsenicale  e  mercuriale 
sulla  sulla  reazione  di  Wassermann,  Gior.  d.  r.  Accad.  di  med.  di 
Torino,  1910,  113. 
Bravetta: 

Ricerche  comparative  sui  recenti  metodi  per  la  diagnosi   della 
sifilide  nelle  malattie  nervose  e  mentali,  (Bollett.  d.  Soc.  med.- 
chir.  di  Pavia,  Dec.  10,  1910. 
Sul  alcuni  metodi  per  la  diagnosi  della  sifilide  nelle  malattie  ner- 
vose e  mentali,  Rassegna  di  studi  psichiatrici,  1911,  i,  5. 


ENGLISH  LITERATURE 

Cadwalader,  W.  B.:  The  Relation  of  Syphilis  to  Progressive  Muscular 
Dystrophy,  N.  Y.  Med.  Jour.,  June  21,  1913. 

Candler:  Wassermann  Reaction  in  General  Paralysis,  Lancet,  Nov.  11, 
1911. 

Candler  and  Mann :  Reliability  of  the  Results  Obtained  by  the  Wasser- 
mann Test  on  Serums  and  Cerebrospinal  Fluids  Obtained  Postmor- 
tem, Brit.  Med.  Jour.,  March  9,  1912. 

Candler  and  Sydney:  Ibid.,  Brit.  Med.  Jour.,  1912,  2671. 

Carlson  and  Martin:  Contribution  to  the  Physiology  of  Lymph.  The 
Supposed  Presence  of  the  Secretion  of  the  Hypophysis  in  the  Cere- 
brospinal Fluid,  Amer.  Jour.  Physiol.,  1911,  29. 

Casamajor,  L.:  An  Unusual  Form  of  Mineral  Poisoning  Affecting  the 
Nervous  System:  Manganese,  Jour,  of  Amer.  Med.  Assoc,  March 
1,  1913. 

Caulfield:  A  Modification  of  Technic  of  Complement-fixation,  Jour,  of 
Med.  Research,  1908,  507. 

Collins  and  Armour:  The  Treatment  of  Syphilitic  Diseases  of  the  Ner- 
vous System  by  Salvarsan,  Jour,  of  Amer.  Med.  Assoc,  1912, 
p.  1918. 

Corbus,  B.  C: 

One  Year's  Experience  with  Salvarsan,  Being  a  Report  of  230  In- 
jections with  Special  Reference  to  Eye  and  Ear  Complications, 
Med.  Record,  Nov.  18,  1911. 
Four  Years'  Experience  with  the  Wassermann  Reaction  in  Prac- 
tice, Jour.  Amer.  Med.  Assoc,  Oct.  5,  1912. 

Corbus  and  Harris:  The  Diagnosis  of  Syphilitic  Eye  Lesions  by  Means 
of  the  Spirochseta  pallida  and  the  Serum  Reaction  of  Wassermann, 
Ophth.  Record,  1909,  296. 


LITERATURE  275 

Coriat: 

The  Cerebrospinal  Fluid  in  Hydrocephalus,  Amer.  Jour,  of  Phys., 
1903,  xii. 

Chemical  Findings  in  the  Cerebrospinal  Fluid,  Amer.  Jour,  of  In- 
sanity, 1904,  vol.  lx,  No.  14,  p.  758. 

The  Production  of  Cholin  from  Lecithin  and  Brain  Tissue,  Amer. 
Jour,  of  Phys.,  vol.  xii,  No.  4,  p.  353,  Dec.  1,  1904. 
Cornell:  The  Cerebrospinal  Fluid  in  Paresis  with  Special  Reference  as 

to  its  Cytology,  Amer.  Jour,  of  Insanity,  1907,  vol.  Ixiv,  p.  73. 
Cotton  and  Ayen:  The  Cytological  Study  of  the  Cerebrospinal  Fluid 

by  Alzheimer's  Method  and  its  Diagnostic  Value  in  Psychiatry, 

Collected  Papers  New  Jersey  State  Hospital  at  Trenton,  1907-11. 
Craig,  C.  F.: 

Observations  Upon  the  Noguchi  Modification  of  the  Wassermann 
Complement-fixation  Test  in  the  Diagnosis  of  Lues  in  the 
Military  Service,  Jour.  Exper.  Med.,  1910,  726. 

Complement-fixation  with  an  Antigenic  Crystal  Obtained  from 
Luetic  Liver,  Jour.  Amer.  Med.  Assoc,  1910,  1264. 

The  Relation  of  Certain  Bacteria  to  Non-specific  Reactions  with 
the  Fixation  Test  for  Lues,  Jour.  Exper.  Med.,  1911,  521. 

The  Immediate  Effect  on  the  Complement-fixation  Test  for  Lues 
of  Treatment  with  Salvarsan,  Arch.  Int.  Med.,  1911,  395. 

Further  Observations  on  the  Complement-fixation  Test  in  Lues, 
Jour,  of  Infect.  Diseases,  1911,  213. 
Craig  and  Nichols:  The  Effect  of  the  Ingestion  of  Alcohol  on  the  Re- 
sult of   the  Complement-fixation  Test  of  Syphilis,   Jour.  Amer. 

Med.  Assoc,  1911,  474. 
Crowe:  Excretion  of  Hexamethylentetramin  in  the  Cerebrospinal  Fluid 

and   its   Therapeutic  Value  in  Meningitis,    Bull.   Johns  Hopkins 

Hosp.,  Baltimore,  April,  1909. 
Cushing,  H.: 

Some  Experimental  and  Clinical  Observations  Concerning  States 
of  Increased  Intracranial  Pressure,  Mutter  Lecture,  1911,  Amer. 
Jour,  of  Med.  Sciences,  Phila.,  1902,  p.  375. 

The  Pituitary  Body  and  its  Disorders,  J.  B.  Lippincott  Co.,  Phila- 
delphia and  London,  1912.    * 

GERMAN  LITERATURE 

Caan:   Ueber   Komplementablenkung   bei   Hodgkinscher   Krankheit, 

Munch.  med.  Woch.,  1910,  1102. 
Calcar:  Zur  Serodiagnostic  der  Syphilis,  Berl.  klin.  Woch.,  1908. 
Cavazzani: 

Ueber  die  Circulation  der  Cerebrospinalfluessigkeit,  Centralblatt  f . 

Phys.,  Oct.  8,  and  Dec.  3,  1892. 
Weiteres  ueber  die  Cerebrospinalfluessigkeit,  Centralbl.  f.  Phys., 
1896,  No.  4. 


276      SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

Cavazzani:  Versuche  ueber  die  Anwesenheit  eines  oxydations  Fermentes 
in  der  Cerebrospinalfluessigkeit,  Centralb.  f.  Phys.,  Dec.  22,  1900. 
Chotzen:     Beitrage    zur    Beurtheilung    der    differentiadiagnostischen 
Verwertbarkeit  der  Lumbalpunction,  Centralbl.  f.  Nervenh.,  1908, 
19. 
Cimbal:  Chemische,  physikalische  und  morphologische  Untersuchungen 
an  240  Spinalpunktionen  und  deren  diagnostische  und  therapeu- 
tische  Verwertung,  Ther.  der.  Gegenw.,  1906,  p.  495. 
Citron: 

Die  practischen  Ergebnisse  der  Sere-diagnostic  der  Syphilis  Ergeb. 

der  inn.,  Med.  u.  Kinderheilk.,  vol.  iv. 
Ueber  Komplementbindungsversuche  bei  infektioesen  und  post- 
infektioesen   Erkrankungen   (Tabes  dorsalis,  etc.),  Deut.  med. 
Woch.,  No.  29,  1907. 
Die  Serodiagnostic   der  Syphilis,    Deut.  med.  Woch.,  1907,   and 

Berl.  klin.  Woch.,  1907. 
Die    Bedeutung   der    Modernen   Syphilisforchung    fuer   die    Be- 

kaempfung  der  Syphilis,  Berl.  klin.  Woch.,  1908,  518. 
Ueber  Aorteninsifficienz  und  Lues,  Berl.  klin.  Woch.,  1908,  2142. 
Komplementbindung,  Eulenberg's  Realencyklop.,  4th  ed.,  1908. 
Ueber  die  Grundlagen   der  biologischen  Quecksilbertherapie  der 
Lues,  Med.  Klin.,  1909. 
Citron  and  Munk:  Das  Wesen  der  W.  R.,  Deut.  med.  Woch.,  1910, 1560. 
Citron  and  Reicher :  Intersuchungen  ueber  das  Fettspaltungsvermoegen 
luetischer  Sera  und  die   Bedeutung  der  Lipolyse  fuer  die  Sero- 
diagnostic der  Lues,  Berl.  klin.  Woch.,  1908,  1398. 
Cohen,  C. :  Die  Serodiagnose  der  Syphilis  in  der  Ophthalmologic,  Berl. 

klin.  Woch.,  1908,  877. 
Csiki,  Michael,  and  Elfer:  Ueber  die  Wirkung  des  Sublimats  bei  der 

W.  R.,  Wien.  klin.  Woch.,  1910,  896. 
Curschmann : 

Ueber  die  therapeutische  Bedeutung  der  Lumbalpunction,  Ther- 

apie  der  Gegenwart,  1912,  242. 
Ueber  artificielle  Drucksteigerung  des  Liquor  cerebrospinalis  als 
Hilfsmittel  bei  der  Lumbalpunction,  Therapie  der  Gegenwart, 
Aug.,  1907. 
Ueber  einige  Indicationen  und  contraindicationen  der    Lumbal- 
punction, Lecture  ref.  in  Munch,  med.  Woch.,  1910,  p.  1308. 

FRENCH  LITERATURE 

Calmette:  M6thode  simple  de  H.  Noguchi  pour  le  sero-diagnostic  de  la 

Syphilis,  La  presse  m£d.,  1909,  No.  26. 
Carriere: 

Meningisme  par  auto-intoxication  gastro-intestinale,  Nord.  m6d., 
June  15,  1902. 

Polynucteose  et  Meningite  tuberculeuse,  Nord.  med.,  June  15, 1902. 

Meningisme  urecemique,  Arch.  Gen.  de  m£d.,  1903,  p.  641. 


LITERATURE  277 

Carriere:  Le  liquid  C.  R.  dans  l'uremie  nerveuse,  Arch.  gen.  de  med., 

Sept.  12,  1905;  C.  R.  Soc.  Biol.,  July  29,  1905. 
Carrieu: 

Les  injections  intra-rachidienes  d'electro  mercurol  dans  le  tabes  et 
le  m^ningo-myelitis  chroniques,  Congr.  internat.  de  med.  de 
Budapesth,  Aug  30,  1909. 

Du  traitement  du  tabes  par  la  rachicentese  et  les  injections  sous 
arachnoidiennes  d'electro-mercurol,  Lecons  cliniques,  premiere 
semestre,  1910,  Montpellier  medical. 

Valeur  diagnostique,  prognostique  et  therapeutique  de  la  ponction 
lumbaire  dans  l'uremie,  Livre  jubilaire  du  Prof.  Lepine,  Lyons, 
Oct.,  1911. 
Carrieu  and  Bousquet:  Le  traitement  du  tabes  par  les  injections  sous 

arachnoidienne  d'electro-mercurol,  Montpellier  med.,  May  1910; 

Provence  med.,  June  11,  1910. 
Cassagne:  Ponction  lombaire  et  Eclampsie,  These  de  Toulouse,  1907, 

p.  766. 
Castaigne:   Toxicite  du    liquide  C.  R.  dans  l'uremie  nerveuse,  C.  R. 

Soc.  Biol.,  Nov.  3,  1900;  Presse  meU,  Nov.  7,  1900. 
Castaigne  and  Debre:  Pneumocoques  abondants  dans  le  liquide  C.  R. 

sans  reaction  cytologique  de  ce  dernier,  Soc.  med.  des  Hop.,  Nov. 

20,  1908. 
Castaigne  and  Weill :  Considerations  pratique  d'ordre  clinique  et  thera- 
peutique sur  le  liquide  C.  R.  des  uremiques,  Jour.  med.  Franc, 

Jan.  15,  1911. 
Cathelin:  Sur  la  circulation  du  liquide  C.  R.,  C.  R.  Soc.  Biol.,  1903, 

p.  1167;  Presse  med.,  No.  90,  Nov.  11,  1903. 
Caussade  and  Vilette: 

Uremie  convulsive  et  comateuse.  Liquide  C.  R.  puriforme,  Soc. 
med.  des  Hop.,  July  24,  1908. 

Uremie  curable,  Soc.  med.  des  Hop.,  1909. 
Cavazzani:  Pression  du  liquide  C.  R.  au  cours  de  crises  6pileptiques, 

Bull.  Accademia  di  Ferrara,  Jan.,  1902. 
Ceconi:  Etude  physico-chimique  du  liquide  C.  R.  normal  et  patholo- 

gique,  Revista  de  clinical  med.,  1905,  Nos.  26  and  30. 
Cesari:  Recherche  de  la  choline  dans  liquide  cerebro-spinale  chez  les 

chiens   soumis  a  l'epilepsie    experimentale,  C.  R.  Soc.  de    Biol., 

Jan.  19,  1907,  p.  66. 
Cestan  and  Ravaut :  Coagulation  en  masse  et  xanthochromic  du  liquide 

C.  R.  dans  un  cas  de  pachimeningomyelite,  Gaz.  des  Hop.,  Sept. 

6,  1904. 
Charrier:  Les  anticorps  syphilitiques  dans  le  liquide  C.  R.  Comple- 
ment a  l'etude  du  liquide  C.  R.  dans  la  Par.  Gen.  et  le  tabes, 

These  de  Paris,  July,  1907. 
Chauffard:  Uremie  aigue  et  polynucleose  rachidienne,  Semaine  med., 

Nov.  13,  1907. 


278     SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

Chauffard  and  Froin: 

Du  diagnostic  differentiel  de  l'hemorragie  meningee  sous-arach- 
noidienne  et  de  la  meningite  cerebro-spinale,  Soc.  med.  des  Hop., 
Oct.,  1903. 

Pachymeningite  hemorragique  avec  chromodiagnostic  sans  hema- 
ties:  hyperthermic  terminate!  Soc.  med.  des  Hop.,  March  27, 
1903. 
Chauffard  and  Vincent:  Meningite  uremique  et  infectieuse,  Soc.  med. 

des  Hop.,  April  15,  1910. 
Chauffard,  Froin,  and  Boidin :  Formes  curables  de  hemorragies  meninges 

arachnoidiennes,  Presse  med.,  June  24,  1903. 
Chauffard,  LaRoche,  and  Grigant:  Le  taux  de  la  eholesterine  dans  le 

liquide  C.  R.  normal  et  pathologique,  Compt.  rend,  de  la  Soc.  de 

Biol.,  1911,  855. 
Claret  and  Lyon-Caen:  Meningite  a  bacille  d'Eberth  au  cours  d'une 

dothienenterie,  Soc.  med.  des  Hop.,  1906. 
Claude:  Polynevrite  alcoohque  ayant  debute  par  un  syndrome  meninge 

avec  coagulation  massive  du  liquide  C.  R.,  Soc.  de  Neurol.,  Nov. 

4,  1909. 
Claude  and  Blanchetiere:  Sur  la  presence  de  la  choline  dans  le  sang  et 

au  cours  de  maladies  du  systeme  nerveux,  Jour,  de  Phys.  et  Pathol. 

general,  vol.  ix,  p.  87,  1907. 
Clemenceau  de  la  Loquerie:    Liquide  C.  R.,  Glycometrie,  These  de 

Paris,  No.  69,  1905,  1906. 
Clergier:  La  ponction  lombaire  de  la  Paral.  Gen.  Sa  valeur  clinique, 

pronostique,  therapeutic,  medico-legale,  These  de  Paris,  No.  285, 

1905. 
Cohen:  De  l'emploi  de  la  reaction  de  fixation  de  Bordet-Gengou  pour 

le  diagnostic  de  la  meningite  cerebro-spinale,  Presse  med.,  Nov. 

6,  1909. 
Concetti:  Rapport  sur  les  meningites  aigues  non  tuberculeuses,  Congres 

de  med.  section  de  maladies  de  l'enfance,  vol.  v,  p.  345,  1900. 
Conos,  B.,  and  Xantopoulos,  C:  Hemorragie  meningee  curable,  valeur 

diagnostique  du  liquide  C.  R.,  L'Encephale,  July  18,  1912. 
Crisafi:   Recherches   et    considerations    cliniques   sur   la   quantite   de 

chlorures  contenue  dans  le  Hquide  C.  R.  des  enfants  malades,  II 

Morgagni,  Jan.,  1904,  No.  1. 
Cruchet:  Permeabilite  meningee  dans  les  meningitis,  C.  R.  de  la  Soc. 

de  Biol.,  1904,  p.  591. 

ITALIAN  LITERATURE 

Calleja,  Camilo:  Alcance  del  Serodiagnosis  con  especial  mencion  del 
metodo  de  Wassermann-Noguchi,  Rev.  Med.  y  Cirug.  pract., 
Madrid,  April,  1909. 

Cavazzani:  Richerche  sulT  Alkalinita  del  hquido  cerebro-spinale, 
Atti  dell'Accademia  di  Ferrara. 


LITERATURE  279 

Comba: 

Sulla  natura  de  la  sustanza  riducata  contenuta  nel  liquido  cefalo- 

rachideo,  Clin.  med.  ital.,  1899,  No.  7. 
Richerche  sulla  quantita  de  azoto  contenuta  nel  liquido  cefalo- 
rachideo,  Clin.  med.  ital.,  1899,  No.  9. 
Crisafi:  Sul  pottere  ossidante  del  liquido  cerebrospinale  di  Bambini 
malati,  Revista  di  clinica  pediatrica,  No.  12,  1903. 

D 
ENGLISH  LITERATURE 

Dean:  An  Examination  of  the  Blood-serum  of  Idiots  by  the  Wasser- 

mann  Reaction,  Lancet,  1910,  p.  227. 
Dixon  and  Halliburton:  The  Action  of  the  Choroid  Plexuses  on  the 

Secretion  of  Cerebrospinal  Fluid,  Jour,  of  Phys.,  March  19,  1910. 
Dochez :  Proteolytic  Enzymes  and  Anti-enzymes  of  Normal  and  Patho- 
logic Cerebrospinal  Fluids,  Jour,  of  Experimental  Medicine,  vol. 

ii,  p.  718,  1909. 
Donaldson:  Studies  of  the  Choroid  Plexus,  Jour,  of  Nerv.  and  Mental 

Dis.,  1907,  p.  720. 
Donath:  Detection  of  Cholin  in  the  Cerebrospinal  Fluid  by  Means  of 

the  Polarising  Microscope,  Medical  News,  N.  Y.,  1905;  also  Jour. 

of  Physiol.,  1905,  p.  211. 
Doree  and   Golla:   Is   Trimethylamin   a   Normal  Constituent  of  the 

Blood,  Urine,  and  Cerebrospinal  Fluid?  Biochem.  Jour.,  1911,  vol. 

v,  p.  306. 

GERMAN  LITERATURE 

Dembrowski:  Zur  Kenntniss  des  Ausfalls  der  W.  R.  bei  Erkrankungen 

des  Nervensystems,  Duet.  med.  Woch.,  1911,  p.  1661. 
Detre:  Ueber  den  Nachweis  von  specifischen  Syphilisantisubstanzen 
und  deren  Antigenen  bei  Lueitikern,  Wien.  klin.  Woch.,  1906,  p. 
619. 
Detre  and  Brezovski:  Serumreaktion  bei  Syphilis,  Wien.  klin.  Woch., 

1908,  1700. 
Dohi:  Ueber  den  Einfluss  von  Heilmitteln  der  Syphilis  auf  die  Immun- 
substanzen  des  Organismus,  Z.  f.  Exp.  Path.  u.  Ther.,  1909,  171. 
Donath,  K.: 

Ueber  die  W.  R.  bei  Aortenerkrankungen  und  die  Bedeutung  der 
provokatorischen  Hg.  Behandlung  fuer  die  serologische  Diag- 
nose der  Lues,  Berl.  klin.  Woch,,  1909,  2015. 
Ueber  den  Werth  der  Lumbalpunktion  fuer   die  Diagnose  und 

Therapie,  Wien.  med.  Woch.,  1903,  No.  19. 
Das  Vorkommen  und  die  Bedeutung  des  Cholins  in  der  Cerebro- 
spinalfluessigkeit  bei  Epilepsie  und  organischen  Erkrankungen 
des  Nervensystems,  nebst  weiteren  Beitragen  zur  Chemie  der- 
selben,  Zeitschr.  f.  phys.  Chem.,  1913,  vol.  xxxix,  p.  526. 


280      SEROLOGY    OF   NERVOUS    AND   MENTAL   DISEASES 

Donath,  K: 

Der  Phosphorsaueregehalt  der  Cerebrospinalfluessigkeit  bei  ver- 

schiedenen,     insbesondere     Nervenkrankheiten,     Hoppe-Seyler, 

Zeitschr.  f.  phys.  Chem.,  1904,  vol.  xlii. 
Fleischmilchsauere  in  der  Eclampsie,  Berl.  klin.  Woch.,   March 

4,  1907. 
Ueber   Choline   in   der    Cerebrospinalfluessigkeit,  Neurologisches 

Centralblatt,  1908,  p.  964;  Zeitschr.  f.  phys   Chem.,  vol.  lxvi, 

1908,  p.  383. 
Ueber  die  Stoffe  die  bei  der  Ausloesung  des  epileptischen  Anfalles 

eine  Rolle  spielen,  Deut.  Zeitschr.  f.  Neryenh.,  1909,  p.  231. 
Zur    Serodiagnostic    der    Meningitis    tuberculosa,    Wien.    klin. 

Rundsch.,  No.  41,  1901. 
Die  Bedeutung  des  Cholins  in  der  Epilepsie,  nebst  Beitragen  zur 

Wirkung  des  ChoUns  und  Neurins,  sowie  zur  Chemie  der  Cere- 
brospinalfluessigkeit,   Duet.    Zeitschr.  f.  Nervenh.,  vol.  xxvii, 

1904. 
Dreuw:  Blutgewinnung  bei  der  W.  R.,  Deut.  med.  Woch.,  1910,  221. 
Dreyer  and  Meirowsky:  Serodiagnostische  Untersuchungen  bei  Pros- 

tituirten,  Deut.  med.  Woch.,  1909,  p.  1698. 
Dreyfus: 

Die  Bedeutung  der  modernen  Untersuchungs  und  Behandlungs- 

methoden   fuer    die   Beurteilung    isolierter  Pupillenstoerungen 

nach  vorausgegangener  Lues,  Munch,  med.  Woch.,  1912,  p.  1647. 
Nervoese  Spaetreaktionen  Syphilitischer  nach  Salvarsan,  Munch. 

med.  Woch.,  1912,  1027. 
Erfahrungen  mit  Salvarsan,  Munch,  med.  Woch.,  1912,  1801. 
Dungern,  Von :  Wie  kann  der  Arzt  die  Wassermannsche  Reaction  ohne 
Vorkenntnisse  leicht  vornehmen?  Miinch.  med.  Woch.,  1911,  p.  507. 
Dungern  and  Hirschfeld:  Ueber  unsere  Modifikation  der  W.  R.,  Miinch. 
med.  Woch.,  1910,  1124. 

FRENCH  LITERATURE 

Danielopolu: 

Sur  une  substance  hemolytique  contenue  dans  le  liquide  C.  R., 

C.  R.  de  la  Soc.  de  Biol.,  vol.  box,  28,  259. 
Seroreaction   de  la  syphilis  dans  les  affections  de  l'aorte  et  des 
arteres,  C.  R.  Soc.  Biol.,  1908,  971. 

Delamare  and  Merle:  Ependymites  aigues  et  subaigues,  Revue  Neurol., 
1910,  p.  333. 

Delaunay:  Contribution  a  l'etude  du  role  des  acides  amines  dans  l'or- 
ganisme  animal,  These  de  Bordeaux,  1910,  p.  29. 

Delmas:  La  ponction  lombaire  chez  le  nouveau-ne,  Prog,  med.,  1912, 
No.  7. 

Demanche  and  Detre:  Valeur  de  la  reaction  de  fixation  pour  le  diag- 
nostic de  la  syphilis  her6ditaire,  C.  R.  Soc.  Biol.,  1910,  696. 


LITERATURE  281 

Demanche  and  Menard:  Valeur  de  la  methode  de  Hecht  pour  le  sero- 
diagnostic  de  la  syphilis;  comparaison  avec  la  reaction  de  Wasser- 
mann,  C.  R.  Soc.  Biol.,  1910,  714. 
Deniges : 

Travaux  recentes  sur  la  reaction  de  Florence,  Bull,  de  la  Soc.  de 

Pharm.  de  Bordeaux,  1900,  p.  104. 
Recherche  microchimique  de  traces  de  trimethylamine.  Identifica- 
tion de  ce  corps,  Bull,  de  la  Soc.   Pharm.  de  Bordeaux,    1908, 
v,  48. 
Deniges  and  Sabrazes:  Sur  la  valeur  diagnostique  de  la  ponction  lom- 
baire.     Examen  comparatif  au  point  de  vue  bacteriologique  et 
clinique  du  liquide  C.  R.,  Revue  de  med.,  1896,  vol.  xvi,  p.  833. 
Deval,  L.:  Sero-reaction  dans  la  Syphihs.     Methode  de  Wassermann 

modifiee  par  Noguchi,  Presse  m6d.,  1909,  937. 
Donath:  Preuve  de  l'existence  de  la  choline  dans  le  liquide  C.  R.  a 
l'aide  du  microscope  polarisant,  Revue  Neurol.,  1906,  No.  4,  p.  145. 
Dopter: 

Le  liquide  C.  R.  dans  la  meningite  cerebrospinale  epidemique,  Le 

Prog,  med.,  1910,  p.  53. 
La  meningite  ourlienne,  Paris  med.,  1910,  35-40. 
Le  liquide  C.  R.  dans  le  coup  de  chaleur,  Soc.  med.  des  Hop.,  Dec. 
4,  1903, 
Drouet:  Meningite  aigua  syphilitique,  These  de  Paris,  No.  24,  1904-05. 
Dubos : 

Du  diagnostic  de  la  P.  G.,  These  de  Montpellier,  No.  75,  1905. 
De  l'absence  de  glycose  dans  le  liquide  C.  R.,  Annal.  med.  psy- 
chol,  1905,  p.  393. 
Ducros:  Etude  sur  le  role  secr^toire  du  liquide  C.  R.  par  le  plexus 

choroides,  These  de  Bordeaux,  No.  45,  1905. 
Ducros  and  Gautrelet :  Presence  de  pigments  biliaires  dans  le  liquide 
C.  R.  apres  suppression  physiologique  des  Plexus  choroides,  C.  R. 
de  la  Soc.  de  Biol.,  1905,  vol.  lviii,  p.  161. 
Duflos:  La  ponction  lombaire  en  psychiatrie,  Paris,  1901. 
Duf  our : 

Memngite  sarcomateuse  diffuse  avec  envahissement  de  la  moelle 
et  des  racines.    Cytologic  positive  et  speciale,  Soc.  Neurologique, 
Jan.  7,  1904. 
Sucre  rachidien,  Soc.  Med.  Hop.,  June  17,  1904. 
Du  liquide  C.  R.  hemorragique  dans  un  cas  d'insolation,  C.  R.  de 

la  Soc.  de  Biol,  February,  1909. 
Des  resultats  de  la  ponction  lombaire   dans   l'insolation,   Rev. 

Neurol.,  vol.  vi,  p.  317,  1909. 
Cytologic  du  liquide  C.  R.  dans  la  meningite  Chronique  Alcoolique, 
Gaz.  hebdomad.,  1901,  p.  1015. 
Dumont,  J.:  La  nouvelle  preparation  arsenicale  d'Ehrlich  (No.  606) 
dans  le  traitement  de  la  syphilis,  Presse  med.,  1910,  636. 


282      SEROLOGY    OF   NERVOUS   AND    MENTAL   DISEASES 

ITALIAN  LITERATURE 

Donzello:  L'esame  batteriologica  del  liquido  cefalo-rachidiano  nella 
puntura  lombare  alia  Quincke,  Riforma  med.,  1900,  vol.  iii,  p.  350. 

E 
ENGLISH  LITERATURE 

Ellis  and  Swift:  The  Cerebrospinal  Fluid  in  Syphilis,  Jour.  Exp.  Med., 

vol.  xviii,  No.  2,  1913. 
Eve:  Some  Motile  Elements  Seen  in  Certain  Cerebrospinal  Fluids,  Brit. 

Med.  Jour.,  1907,  p.  1399. 

GERMAN  LITERATURE 

Edel:  Die  W.  R.  bei  der  progessiven  paralyse  und  paralyse  aehnlichen 

Erkrankungen,  Ref.  in  Allg.  Zeitschr.  f.  Psych.,  1909,  pp.  217-223. 

Ehlers:  Ehrlich's  606  gegen  Lepra,  Munch,  med.  Woch.,  1910,  2141. 

Ehrlich,  H.:  Einige  Beitrage  von  Wassermannschen  Syphilisreaktion, 

Wien.  med.  Woch.,  1910,  No.  22. 
Ehrlich,  Paul: 

Gesammelte  Arbeit  aus  dem  Gebiete  der  Immunitaetsforschung, 

1904. 
Bietet  die  intravenoese  Injektion  von  606  besondere    Gefahren, 

Munch,  med.  Woch.,  1910,  1826. 
Beitrage  zur  experimentellen  Pathologie  und  Chemotherapie,  Leip- 
zig, 1909. 
Chemotherapie  von  Infektionskrankheiten,  Ztschr.  f.  aerzt.  Fort- 

bildung,  1909,  721. 
Die  Salvarsantherapie,  Munch,  med.  Woch.,  1911,  Iviii. 
Ehrlich  and  Hata:  Die  experimentelle  Chemotherapie  der  Spirilosen, 

Berlin,  Julius  Springer,  1910. 
Ehrmann  and  Stern:  Mittheilungen  zur  W.  R.,  Berl.  klin.  Woch.,  1910, 

283. 
Eichelberg: 

Die  Serumreaktion  auf  Lues  mit  besonderer   Beruecksichtigung 
ihrer  praktischen  Verwertbarkeit  fuer  die  Diagnostic  der  Ner- 
venkrankheiten,  Deut.  Zetschr.  f.  Nervenh.,  1909,  pp.  319-341. 
Die   Bedeutung  der  Untersuchung  der  Cerebrospinalfluessigkeit, 

Med.  Klin.,  1912,  p.  1187. 
Die  praktische  Verwertbarkeit  der  W.  R.  auf  Lues,  und  das  Vor- 
kommen  derselben  bei  Scharlach,  Munch,  med.  Woch.,  1908, 
1206. 
Eichelberg  and  Pfoertner:  Die  praktische  Verwertbarkeit  der  verschie- 
denen  Untersuchungsmethoden  des  Liquor  cerebrospinalis  fuer  die 
Diagnostic   der   Geistes  und   Nervenkrankheiten,   Monatschr.  f. 
Psych,  u.  Neurologie,  1909,  pp.  486-497. 


LITERATURE  283 

Eisler:  Ueber  Komplementablenkung  und  Lezithinausflockung,  Wien. 

klin.  Woch.,  1908,  p.  422. 
Eitner: 

Ueber  den  Nachweis  von  Antikoerpern  im  Serum  eines  Lepra- 
kranken  mittels  Komplementablenkung,  Berl.  klin.  Woch.,  1906, 
p.  1555. 
Zur  Frage  der  Anwendung  der  Komplementbindungsreaktion  auf 
Lepra,  Wien,  klin.  Woch.,  1908,  p.  729. 
Elias,  Neubauer,  Porges,  and  Salomon: 

Theoretisches  ueber  die  Serumreaktion  auf  Syphilis,  Wien.  klin. 

Woch.,  1908,  p.  376. 
Ueber  die  Methodik  und  Verwendbarkeit  der  Ausflockungsreak- 
tion  fuer  die  Serodiagnose  der  Syphilis,  Wien.  klin.  Woch.,  1908, 
p.  831. 
Eliasberg:  Zur  Theorie  und  Praxis  der  W.  R.,  St.  Petersburger,  Med. 

Woch.,  1910,  xxvii. 
Engel:  Ueber  die  Sekretionserscheinungen  in  den  Zellen  des  Plexus 

Choroides  des  Menschen,  Arch.  f.  Zellforschung,  1909. 
Epstein  and  Pribram : 

Wirkung  des  Sublimate  auf  die  komplexe  Haemolyse  durch  immun- 
serum  und  die  W.  R.,  Ztschr.   f.  Exp.  Path,  and  Ther.,  1909- 
10,  549. 
Zur  Frage  des  Zusammenhanges  zwischen  W.  R.  und  Hg.  Behand- 
lung,  Wien.  klin.  Woch.,  1910,  290. 
Erb :  Ueber  die  Diagnose  und  Fruehdiagnose  der  Syphilogenen  Erkrank- 
ungen  des  Zentralnervensystems,   Deut.  Zeit.  f.  Nervenh.,  1907, 
p.  425. 

FRENCH  LITERATURE 

Ehlers  and  Bourret:  La  reaction  de  Wassermann  dans  la  Lepre,  Mitteil. 

und  Verhandl  der  II.  internation.  wissenschaftl.  Lepra-Konference, 

III,  368. 
Enriquez  and  Sicard:  Les  oxydations  de  l'organisme  (Oxydases),  Actual- 

ites  med.  BaUiere  fils,  Paris,  1902. 
Esmein  and  Paru :  Diagnostic  de  la  nature  syphilitique  de  certaines 

cirrhoses  du  foie  par  la  seroreaction  de  Wassermann;  recherche 

comparee  des  anticorps  dans  le  serum  et  l'ascite,  C.  R.  Soc.  Biol., 

1909,  159. 
Espinet:  Polynucleose  rachidienne  et  nleningite  tuberculeuse,  These  de 

Paris,  No.  28,  Nov.,  1908. 
Euzier:  Paralysie  generale  et  Tabes,  Montpelher  Med.,  1910. 
Euzier,  Mestrezat,  and  Roger:  La  reaction  du  liquide  C.  R.  a  l'acide 

butyrique  (Reaction  de  Noguchi)  sa  valeur  dans  le  diagnostic  de 

syphilid  du  n6vraxe,  L'Encephale,  September,  1911,  No.  9. 


284      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 


ENGLISH  LITERATURE. 

Famulener  and  Alice  Mann:  Experimental  Data  Relating  to  Hemolytic 
Sera,  Collected  Studies  from  the  Research  Lab.  Dept.  of  Health, 
City  of  N.  Y.,  1908-09,  p.  161. 
Farnell:  The  Cerebrospinal  Fluid;  its  Cellular  Elements  and  Globulin 

Content,  Amer.  Jour,  of  Insanity,  1911,  p.  23. 
Feiling,  A. :  The  Blood  and  the  Cerebrospinal  Fluid  in  Mumps,  Lancet, 

July  12,  1913. 
Fitzgerald,  J.  S. :  A  Few  Remarks  on  Serum  Diagnosis  of  Syphilis,  N.  Y. 

Med.  Jour.,  1910,  221. 
Fleischman  and  Butler:  Serum  Diagnosis  of  Syphilis,  Jour.  Amer.  Med. 

Assoc,  1907,  934. 
Fleming,  A.:  A  Simple  Method  of  Serum  Diagnosis  of  Syphilis,  Lancet, 

1909,  1512. 
Forbes:  A  Note  on  the  Cerebrospinal  Fluid  in  Acute  Poliomyelitis, 

Lancet,  Nov.  18,  1911. 
Fordyce,  J.  A.: 

Further  Observations  On  the  Use  of  the  Ehrlich-Hata  Preparation 

606  in  the  Treatment  of  Syphilis,  N.  Y.  Med.  Jour.,  1910,  957. 

The  Administration  of  Salvarsan  in  Syphilis,  Jour.  Amer.  Med. 

Assoc,  Oct.  5, 1912. 

Foster:  Sugar  in  the  Cerebrospinal  Fluid  in  Diabetes,  Boston  Med.  and 

Surg.  Jour.,  1906,  p.  441. 
Fox,  Howard: 

The  Principles  and  Technic  of  the  Wassermann  Reaction  and  its 

Modifications,  Med.  Rec,  1909,  421. 
A  Comparison  of  the  Wassermann  and  Noguchi  Complement-fixa- 
tion Tests,  Jour,  of  Cutan.  Dis.,  1909,  338. 
The  Relative  Value  of  Mercury  and  Salvarsan  from  a  Serologic 

Point  of  View,  Jour.  Amer.  Med.  Assoc,  Oct.  5,  1912. 
The  Wassermann  and  Noguchi  Complement-fixation  Test  in  Lep- 
rosy, Amer.  Jour.  Med.  Sciences,  1910,  724. 
The  Wassermann  Reaction  (Noguchi   Modification)  in  Pellagra, 
N.  Y.  Med.  Jour.,  1909,  1206. 


GERMAN  LITERATURE 

Facchini:  Beitrage  zur  Technik  der  Wassermannschen  Reaktion,  Z.  f. 

Immunitaetsforchung,  1909,  257. 
Fankhauser: 

Erfahrungen  ueber  Lumbalpunktion  bei  Geisteskranken,  Korre- 

spondenzblatt  f.  Schweizer  Aerzte,  1907,  p.  33. 
Zur  Technik  der  Zaehlung  der   zelligen    Elemente    des    Liquor 
cerebrospinalis,  Zeitschr.  f.  ges.  Ner.  u.  Psy.,  1910,  p.  341. 


LITERATURE  285 

Fauser: 

Zyto  und  Serodiagnostic  und  ihre  Bedeutung  fuer  die  Neurologic, 

Ref.  in  Deut.  med.  Woch.,  1909,  p.  1460. 
Ueber  den  heutigen  Zustand  der  Diagnostik  und  differentialdiag- 
nostik  der  luetischen  und  metaluetischen  Gehirnerkrankungen, 
Fortschr.  d.  Med.,  1910,  xxviii,  Nos.  14,  15,  16. 
Favente:  Ueber  156  mit  Ehrlich-Hata  606  behandelte  Faelle,  Munch. 

med.  Woch.,  1910,  2080. 
Faworsky:    Zur    chemischen  und  cytologischen  Untersuchungen  der 
Lumbalfluessigkeit   bei    Nervenkranken,   Rousski  Vratsch,   1910, 
p.  756. 
Fischer,  O: 

Zur  Frage  der  Zytodiagnose  der  Progressiven   Paralyse,    Prager 

med.  Woch.,  1904,  p.  515. 
Klinische  und  anatomische  Beitrage  zur  Frage  nach  den  Ursachen 
und  der  Bedeutung  der  cerebrospinalen  Pleocytose  (der  Zellver- 
mehrung  im  Liquor  cerebrospinalis),  Jahrbuch  f .  Psy.  und  Neu- 
rol., 1906,  No.  27. 
Die  anatomische  Grundlage  der  cerebrospinalen  Pleocytose,  Monat- 

schr.  f.  Psy.  u.  Neurol.,  1910,  p.  512. 
Flatau:  Ueber  Xanthochromic  und  Bildung  eines  fibrinoesen  Coag- 
ulums  im  Liquor  cerebrospinalis,  Neurologia  polska,  1910,  No.  6. 
Fischer,  W.: 

Klinische  Betrachtungen  ueber  die  W.  R.  bei  Syphilis,  Berl.  klin. 

Woch.,  1908,  151. 
Die  Wassermannsche  Syphilisreaction  und  ihre  diagnostische  und 

therapeutische  Bedeutung,  Ther.  d.  Gegenw.,  1908,  168. 
Die  Bewertung  der  Wassermannschen  Reaction  fuer  die  Frueh- 
diagnose    und   die   Therapie   der   Syphilis,   Med.   Klin.,   1909, 
176. 
Fischer  and  Meier:  Ueber  den  klinischen  Wert  der  Wassermannschen 

Serodiagnostik  bei  Syphilis,  Deut.  med.  Woch.,  1907,  2169. 
Fleischer :  Cytodiagnostische  Untersuchungen  des  Liquor  cerebrospinalis 
bei  Augenkranken,  Vereinsbeilage  der  Deut.  med.  Woch.,  1908, 
p.  1615. 
Fleischmann:  Die  Theorie,  Praxis,  und  Resultate  der  Serumdiagnostik 

der  Syphilis,  Derm.  Zentralbl.,  1908,  pp.  226-239. 
Fornet  and  Schereschewsky:  Serodiagnose  bei  Lues,  Tabes,  und  Para- 
lyse, Munch,  med.  Woch.,  1907,  1471. 
Foster  and  Tomasczewski :  Nachweis  von  lebenden  spirochaeten  im 

Gehirn  von  paralytikern,  Deut.  med.  Woch.,  1913,  xxxix,  1237. 
Fraenkel,  E.:  Ueber  das  Verhalten  des  Gehirns  bei  akuten  Infektion3- 

krankheiten,  Virch.  Arch.,  Beiheft  Z,  194,  1908. 
Fraenkel  and  Much,  H.: 

Die  W.  R.  an  der  Leiche,  Munch,  med.  Woch.,  1908,  p.  2479. 
Ueber  die  Wassermannsche  Serodiagnostik  der  Syphilis,  Munch, 
med.  Woch.,  1908,  p.  662. 


286      SEROLOGY   OF   NERVOUS   AND   MENTAL  DISEASES 

Fraenkel,  Heiden: 

Zur  Cytodiagnose  der  Tabes,  Neurol.  Zentralb.,  1903,  p.  1135. 

Zur  Chemie  der  Cerebrospinalfluessigkeit,  Biochem.  Zeitschr.,  1907, 
p.  188. 

Liquor  cerebrospinalis  und  Wassermannsche  R.,  Neurol.  Zentralb., 
Jan.  16,  1912. 

Die  Zellen  der  Cerebrospinalfluessigkeit  in  ungefaerbtem  Zustande, 
Neurol.  Zentralb.,  1912,  vol.  xxxi. 
Fraenkel,   M.:    Weitere    Beitrage  zur   Bedeutung  der  Auswertungs- 

methode    der    Wassermannschen    Reaction    im    Liquor    cerebro- 
spinalis an  der  Hand  von  32  klinisch  und  anatomisch  untersucbten 

Faellen.   Ueber  das  Vorkommen  der  Wassermann  Reaction  im 

Liquor    cerebrospinalis    bei    Faellen  von   friscber  primaerer   und 

secundaerer   Syphilis,    Zeitschr.  f.   d.  gesamm.   Neurol,  u.  Psy., 

1912,  vol.  ii,  1  and  2. 
Fraenkel  and  Grouven:  Erfahrungen  mit  dem  Ehrlichschen  Mittel 

606,  Miinch.  med.  Woch.,  1910,  1771. 
Frankl,  O.:  Beitrage  zur  Lehre  von  der  Vererbung  der  Syphihs,  XIII 

Kongres  der  deut.  Gesel.  f.  Geburtshilfe  u.  Gynek.,  June,  1909; 

also  Monatschr.  f.  Geburtshilfe  u.  Gynek.,  1910,  xxxd,  340. 
Freudenberg:   Eine   Mahnung   zur  Forsicht  beit   der   diagnostischen 

Verwertung   der  Wassermannschen   Syphilisreaktion,  Berl.   klin. 

Woch.,  1910,  1231. 
Frey:  Ueber  die  Wirkung  des  Enesol  auf  die  metalueitischen  Nerven- 

erkrankungen    und    auf    die   W.    R.,    Berl.   klin.    Woch.,    1911, 

1171. 
Freyham:  Ein  Fall  von  Meningitis  tuberculosa  mit  Ausgang  in  Heilung, 

Deut.  med.  Woch.,  1896,  No.  35. 
Friedberger : 

Ueber  die  Haltbarmachung  der  Komplemente,  Berl.  klin.  Woch., 
1907,  1299. 

Ueber  das  Verhalten  der  komplemente  in  hypertonischen   Salz- 
loesungen,  Centralb.  f.  Bakt.,  1908,  441. 

Ueber  Haltbarmachung    der    Komplemente,    Berl.   klin.  Woch., 
1907,  1299. 
Friedlander:  Der  wert  der  W.  R.  fuer  die  Diagnose  der  Syphihs,  Arch. 

f.  Dermatologie  und  Syph.,  1910,  255. 
Fritz  and  Kren:  Ueber  den  Wert  der  Serumreaction  bei  Syphihs  nach 

Porges,  Meier  and  Klausner,  Wien.  klin.  Woch.,  1908,  386. 
Froederstroem  and  Wigert:  Ueber  das  Verhaeltniss  der  W.  R.  zu  den 

Zytologischen     und     chemischen     Untersuchungsmethoden     der 

Spinalfluessigkeit,  Monatschr.  f.  Psy.,  1910,  vol.  xxviii. 
Frugoni   and   Pisani:   Vielfache   Bindungseigenschaften   des   Komple- 

mentes  einiger  Sera  (Leprakranker)   und  ihre  Bedeutung,  Berl. 

khn.  Woch.,  1909,  1530 
Fua  and  Koch:  Zur  Frage  der  W.  R.  bei  Scharlach?  Wien.  klin.  Woch., 

1909,  522. 


LITERATURE  287 

Fuchs:  Ueber  Beobachtungen  an  Flimmerzellen,  Anat.,  Heft  von  Merkel 

and  Bonnet,  1904,  p.  77. 
Fuchs  and  Rosenthal:  Physikalische,  chemische,  zytologische  und  ander- 

weitige  Untersuchungen  der  Zerebrospinalfluessigkeit,  Wien.  med. 

Presse,  1904,  p.  2061. 
Fuerbringer:  Zur  klinik  der  Lumbalpunktion,  Kongr.  f.  inn.  Med., 

1897,  p.  331. 
Fumarola  Tramonti:   GlobuHnreaction,    Albuminreaction,    und   Lym- 

phocytose  bei  den  organischen  Erkrankungen  des  Nervensystems, 

Monatschr.  f.  Psy.  und  Neurologie,  1911,  vol.  xxx. 
Fiith  and  Lockemann:  Ueber  den  Nachweis  von  Fleischmilchsauere 

in   der   Cerebrospinalfluessigkeit   Eklamptischer,   Arch.   f.   Gyn., 

1905,  76. 

FRENCH  LITERATURE 

Ferrier:  Cytologie  du  hquide  C.  R.  dans  la  Leucemie,  C.  R.  de  la  Soc. 

de  Biol.,  1908,  803. 
Feuille:  Etude  sur  1'albumine  et  la  cytolyse  du  hquide  C.  R.,  Soc.  med. 

des  Hop.,  April  27,  1906. 
Fiessinger  and  Marie:  Le  ferment  proteolytique  des  leucocytes  dans 

^es  meningites  aigues  et  meningocoques,  Compt.  rend,  de  la  Soc. 

Biol.,  1909,  915. 
Foix:  Technique  simplifiee  de  reaction  de  fixation,  C.  R.  Soc.  Biol., 

July,  1909;  Semaine  meU,  1909,  359. 
Follet  and  Chevrel:  H6morragies  sous-arachnoidiennes  spontanees  chez 

des  jeunes  gens.  Nouvel  example  de  biligenie  hemolytique,  Gaz. 

des.  Hop.,  April  5,  1910. 
Folty,  C.:  Etudes  sur  le  liquide  C.  R.,  Gaz.  meU  de  Paris,  1855,  p.  114. 
Fornaca:  Coagulation  et  xanthochromic  du  hquide  C.  R.  dans  un  cas 

de  m^ningo-myelite  de  la  queue  de  cheval,  Gazzette  degh  Ospedale 

e  deUe  Cliniche,  August  4,  1906. 
Francis:  Le  hquide  c6phalo-rachidien,  Progres  mid.,  1910,  376. 
Froin: 

Inflamations  meninges  avec  reaction  chromatique,  fibrineuse  et 
leucocytique  du  hquide  cephalo-rachidien,  Gaz.  des  Hop.,  Sep- 
tember 3,  1903. 

Le  liquide  C.  R.  dans  l'h6morragie  c6r£bromeningee,  Gaz.  des 
Hop.,  Nov.,  1903. 

Les    h^morragies    sous-arachnoidiennes    et    le    mechanisme    de 
l'Hematolyse  en  general,  These  de  Paris,  Dec,  1904,  No.  113. 
Froin  and  Ramond:  Evolution  des  reactions  cellulaires  et  s6ro-fibrin- 

euses  dans  le  hquide  C.  R.  retire  par  ponction  lombaire  des  menin- 
gites tuberculeuses,  C.  R.  Soc.  de  Biol.,  Nov.  11,  1905. 
Froment:  Diagnostic  et  pronostic  de  l'uremie  nerveuse  par  le  dosage 

de  l'urde  dans  le  hquide  C.  R.,  Lyon  meU,  February  6,  1910. 


288      SEROLOGY    OF    NERVOUS    AND    MENTAL   DISEASES 

ITALIAN  LITERATURE 

Forbes,  G.:  Pathologie  du  liquide  C.  R.,  Lavore  Revista  di  Clinica  e 
Microscopia  Clinica,  Oct.  and  Nov.,  1908. 


ENGLISH  LITERATURE 

Gay: 

The  Fixation  of  Alexins  by  Specific  Serum  Precipitates,  Centralb. 

f.  Bact.,  1905,  xxii,  522. 
Studies  in  Immunity,  Wiley  &  Sons,  N.  Y.,  1909. 

Gay  and  Fitzgerald:  The  Serum  Diagnosis  of  Syphilis,  Boston  Med. 
and  Surg.  Jour.,  1909,  432. 

Gibbs  and  Wansey:  Preliminary  Note  on  the  Comparative  Value  of 
the  Various  Methods  of  Antisyphilitic  Treatment  Estimated  by 
the  Wassermann  Reaction  and  Clinical  Observation,  Lancet,  1910, 
1256. 

Goetsch,  Cushing,  and  Jacobson :  Carbohydrate  Tolerance  and  the  Pos- 
terior Lobe  of  the  Hypophysis  Cerebri,  Bull.  Johns  Hopkins  Hosp., 
1911,  pp.  165-190. 

Gottheil,  W.  S.:  Experiences  with  Arsenobenzol,  Med.  Rec,  1910,  1174. 

Gradwohl:  The  Luetin  Test  for  Syphilis.  A  Preliminary  Report  of 
44  Cases,  Med.  Rec,  1912,  973. 

Gregory  and  Karpas:  A  Case  of  Cerebral  Syphilis  Occurring  Six 
Months  After  the  Initial  Lesion;  Review  of  Neurology  and 
Psychiatry,  May,  1913. 

Groat,  W.  A.:  The  Serum  Diagnosis  of  Syphilis,  Using  the  Noguchi 
System,  N.  Y.  Med.  Jour.,  1910,  p.  954. 

Grulee  and  Moody:  Lange's  Colloidal  Gold  Chlorid  Test  on  Cere- 
brospinal Fluid  in  Congenital  Syphilis,  Jour.  Amer.  Med.  Assoc, 
July  5,  1913. 

GERMAN  LITERATURE 

Geissler:   Eine   objektive    Methode   zur   Bestimmung   pathologischer 

Zellvermehrung    im  Liquor  cerebrospinalis,  Munch,  med.  Woch., 

1911,  No.  36. 
Gelarie,   A.:  Ueber  die  diagnostische  und  therapeutische  Bedeutung 

der  W.  R.  und  die  Brauchbarkeit  der  Modifikation  Hecht,  Arch. 

f.  Dermat.  u.  Syph.,  1910,  266. 
Gennerich:   Ueber    Syphilisbehandlung    mit    Ehrlich    606,    Berl.  klin. 

Woch.,  1910,  1735. 
Gerhardt:   Ueber  die  diagnostische  und  therapeutische  Bedeutung  der 

Lumbalpunktion,  Mitt.  a.  d.  Grenzgeb.  d.  Med.  u.  Chir.,  1904,  13. 
Geronne,  Hr.:    Ueber    die    Wirkung    des    Ehrlich-Hataschen    Arsen- 

praeparates  auf  menschliche  Syphilis,  Berl.  klin.  Woch.,  1910,  1338. 
Ghon,  Mucha,  and  Mueller :  Zur  Aetiologie  der  acuten  Meningitis,  Cen- 

tralblatt  fuer  Bakteriologie  und  Parasitenkunde,  vol.  xli. 


LITERATURE  289 

Gianuzzi:    Beitrage   zum   Studium    der    Cytodiagnose,    Wien.    med. 

Blaetter,  1903,  47. 
Gjorgjevic  and  Savnik:  Ueber  die  W.  R.  bei  Lues  und  bei  Psoriasis 

vulgaris,  Wien.  klin.  Woch.,  1910,  1264. 
Glaser,  F.:  Die  Erkennnng  der  Syphilis  und  ihrer  aktivitaet  durch 

probatorische  Hg.  Injektionen,  Berl.  klin.  Woch.,  1910,  1264. 
Glaser  and  Wolfssohn:  Klinische  Beobachtungen  ueber  die  Wasser- 
mann-Neisser-Brucksche    Reaktion    und    deren    Kontrolle    durch 
Sektionsresultate,  Med.  Klin.,  1909,  1731. 
Glueck:  Kurzer  Bericht  ueber  109  mit  "606"  behandelte  Luesfaelle, 

Mtinch.  med.  Woch.,  1910,  1638. 
Goldschmidt   and   Pribram:    Wirkung  der    Narkotika  und  Alkaloide 
auf  das  Komplement,   Zeitschr.  f.  Exper.   Path.  u.  Ther.,  1909, 
211. 
Gross,  S.,  and  Volk,   R.:  Weitere  Serodiagnostische  Untersuchungen 

bei  Syphilis,  Wien.  klin.  Woch.,  1908,  1522. 
Grosz,  Emil  V. : 

Arsenobenzol  (EhrHch  606)  gegen  syphilitische  Augenleiden,  Deut. 

med.  Woch.,  1910,  1698. 
Bemerkungen    zur    Mitteilung    von    R.    Bauer    u.    A.  Hirsch. 

Beitrage  zum  Wesen  der  W.  R.,  Wien.  klin.  Woch.,  1910,  103. 
Schlussbemerkung  zu  der  Entgegnung  von  R.  Bauer  u.  A.  Hirsch, 
Wien.  klin.  Woch.,  1910,  171. 
Grouven,  Karl:  Beginn  und  Dauer  der  Arsenausscheidung  im  Urin 
nach  Anwendung  des  Ehrlich-Hataschen  praeparates  Dioxydia- 
midoarsenobenzol,  Miinch.  med.  Woch.,  1910,  2079. 
Gruenberger:  Ueber  den  Befund  von  Acetessigsauere  in  der  Cerebro- 
spinalfluessigkeit   bei  Coma  Diabeticum,  Zeitschr.   f.  Inn.  med., 
1905,  617. 
Gulewitsch : 

Ueber  Choline  und  einige  Verbindungen,  Zeitschr.  f .  Phys.  Chemie, 

1898,  vol.  xxiv,  p.  513. 
Choline   in   der   normalen   und   pathologischen   Spinalfluessigkeit 
und  deren  physiologische  Funktion,  Kongress  f .  inn.  Med.,  April, 
1900. 
Gumprecht: 

Gefahren  bei  der  Lumbalpunction,  ploetzliche  todesfaelle  danach, 

Deut.  med.  Woch.,  1900,  24. 
Cholin    in    der   normalen   und    pathologischen    Spinalfluessigkeit 
und  die  physiologische  Funktion  derselben,  XVIII  Kongress  f. 
innere  med.,  1900. 

FRENCH  LITERATURE 

Gaston  and  Girauld:  Sero-diagnostic  (Reaction  de  Wassermann)  chez 
un  malade,  atteint  de  chancre  syphilitique  de  l'amygdale,  Bull, 
de  la  Soc.  Franc,  de  Dermat.  et  de  Syph.,  1908,  235. 
19 


290      SEEOLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

Gaston  and  Lebert:  Sero-diagnostic  de  la  syphilis.    Reflections  sur  la 

technique  et  la  valeur  des  methodes,  a  propos  de  200  cas,  Bull. 

de  la  Soc.  Franc,  de  Dermat.  et  de  Syph.,  1910,  199. 
Gaucher  and  Abrami:  Le  sero-diagnostic  des  formes  atypiques  de  la 

lepre,  Bull,  de  la  Soc.  med.  des  Hop.  de  Paris,  1908,  p.  497. 
Gaucher   and   Merle:   Constatation   du  treponema  pallidum  dans  le 

liquide  C.  R.  au  cours  de  la  syphilis  acquise  des  centres  nerveux, 

C.  E.  de  l'Acad.  des  Sci.,  148,  13,  862. 
Gay:  La  deviation  de  l'alexine  dans  l'hemolyse,  Ann.  Inst.  Pasteur, 

1905,  539. 
Gilbert  and  Castaigne:  Le  liquide  C.  R.  dans  la  cholemie,  Presse  m<§d., 

Nov.  3,  1901. 
Gillard:  Le  glucose  dans  le  liquide  C.  R.,  These  de  Lyon,  1904,  No.  67. 
Giraudet:    Complications   meningitiques   de   la   fievre   typhoide   chez 

l'enfant,  These  de  Bordeaux,  1905,  No.  27. 
Greco:  Sur  le  pouvoir  reducteur  du  liquide  C.  R.,  Revue  d'hygiene  et 

de  medicine  infantiles,  1909,  p.  353. 
Grimbert  and  Coulaud:  Caracterisation  du  glucose  dans  le  liquide  C. 

R.,  C.  R.  Academie  des  sciences,  February,  1903. 
Guillain  and  Parant:  Presence  d'albumine  coagulable  par  la  chaleur  dans 

les  liquides  de  paraplegiques  spinaux,  Soc.  Neurol.,  April  2,  1903. 
Guinard :  La  ponction  lombaire  et  le  fractures  du  crane,  Jour,  de  Med. 

de  Paris,  1910,  No.  28. 
Guinon  and  Paris:  Paralyse  infantile  avec  reaction  meningee,  C.  R.  de 

la  Soc.  des  Hop.  de  Paris,  1903,  673. 
Guinon  and  Rist :  Deux  cas  de  poliomyelite  anterieure  aigue  sans  reaction 

meningee  cytologique,  Ibid. 

ITALIAN  LITERATURE 

Gonzales  and  Verga:  Nota  sul  liquido  C.  R.  nei  Pazzi,  Archiv.  delle 
Malattie  mentali,  1890,  p.  23. 

H 

ENGLISH  LITERATURE 

Halliburton: 

On  Cerebrospinal  Fluid,  Jour,  of  Physiol.,  1889,  vol.  x,  p.  176. 
Choline,  Folia  Neurologica,  1907,  p.  33. 
Halliburton,  Thompson,  and  Hill:  Observations  on  the  Cerebrospinal 
Fluid  of  Man,  Proc.  of  the  Royal  Soc.  of  London,  1899,  vol.  briv, 
p.  343;  Lancet,  1898,  No.  9. 
Hand: 

The  Diagnostic  Value   of  Chemical   and   Bacteriologic  Analyses 

of  Cerebrospinal  Fluids,  Amer.  Pediatr.  Soc,  May  25,  1908; 

Medical  Record,  Sept.  26,  1908,  p.  544. 

The  Positive  Diagnosis  of  Meningitis,  Particularly  Tuberculous, 

by  Means  of  Lumbar  Puncture,  Phila.  Med.  Jour.,  1902,  p.  292. 


LITERATURE  291 

Heiman:  Lumbar  Puncture  in  Infants;  Measurement  of  the  Cerebro- 
spinal Pressure,  New  York  Med.  Jour.,  Nov.  17,  1906. 

Heimann,  W.  J.: 

A  Method  for  the  Mathematical  Reading  of  the  Original  Wasser- 

mann  Reaction,  Jour.  Amer.  Med.  Assoc,  May  21,  1910. 
The  Wassermann  Reaction  and  the  Physician,  N.  Y.  State  Med. 

Jour.,  July,  1911. 
Present  Day  Diagnosis  of  Acquired  Cutaneous  Syphilis,  Amer. 
Jour,  of  Urology,  March,  1912. 

Hemenway:  The  Constant  Presence  of  Tubercle  Bacilli  in  the  Cerebro- 
spinal Fluid  of  Tuberculous  Meningitis,  with  Observations  on  the 
Cerebrospinal  Fluid  in  Other  Forms  of  Acute  Meningitis,  Amer. 
Jour,  of  Diseases  of  Children,  1911,  p.  37. 

Hough :  Remarks  on  the  Comparative  Diagnostic  Value  of  the  Noguchi 
Butyric  Acid  Reaction  and  the  Cytologic  Examination  of  the  Cere- 
brospinal Fluid,  Bull.  No.  2,  Government  Hosp.  for  Insane,  Wash- 
ington, 1910,  118. 

Hough  and  Laf ora :  Some  Findings  in  the  Cerebrospinal  Fluid  in  Eleven 
Cases  of  Acute  Anterior  Poliomyelitis,  Epidemic  Form,  Folia  Neuro- 
biologica,  1911,  No.  5,  p.  3. 

GERMAN  LITERATURE 
Halberstaedter :  Die  Bedeutung  der  neueren  Hilfsmittel  fuer  die  Diag- 

nostik   und   Therapie    der    Syphilis,    Therap.    Monatsch.,    1910, 

xxiv,  64. 
Halberstaedter,  E.  Mueller,  and  Reiche:  Ueber  Komplementbindung 

bei  Syphilis  hereditaria,  Scharlach  und  anderen  Infektionskrank- 

heiten,  Berl.  klin.  Woch.,  1908,  p.  1917. 
Hald:  Zur  permeabilitaet  der  Leptomeningen  besonders  Hexamethylin 

tetramin  gegenueber,  Arch.  f.  exper.  Pathol,  u.  Pharmak.,  1911, 

Nos.  5  and  6. 
Hartwich:  Bacterium  Coli  im  Liquor  cerebrospinalis,  Berl.  klin.  Woch., 

1911,  795. 
Hata:  Chemotherapie  der  Spirilosen,  Munch,  med.  Woch.,  1910,  9S1. 
Hauck:  Positiver  Ausfall  der  W.  R.  bei  Lupus  erythematoss  acutus, 

Munch,  med.  Woch.,  1910,  lvii,  17. 
Hauptmann : 

Serologische  Untersuchungen  von  Familien  syphilogener  Nerven- 
kranke,  Zeitschr.  f.  d.  ges.  Neurol,  u.  Psy.,  1911,  No.  8. 

Eine  biologische  Reaktion  im  Liquor  cerebrospinalis  bei  organ- 
ischen  Nervenkrankheiten,  Med.  Klin.,  1910,  No.  6,  p.  181. 

Die  Vorteile  der  Verwendung  groesserer  Liquormangen  (Auswer- 

tungsmethode)  bei  der  Wassermannschen  Reaktion  fuer  die  Neu- 

rologische  Diagnostik,  Deut.  Zeitschr.  f.  Nervenheilk.,  1911,  240. 

Hauptmann  and  Hoessli:  Erweiterte  Wassermannsche  Methode  zur 

Differentialdiagnose  zwischen  Lues  cerebrospinalis  und  multipler 

Sklerose,  Munch,  med.  Woch.,  1910,  No.  30. 


292      SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

Hecht: 

Eine  Vereinfachung  der  Komplementbindungsreaktion  bei  Syph- 
ilis, Wien.  klin.  Woch.,  1908,  p.  1742,  No.  50. 
Untersuchung  ueber  haemolytische,  eigenhemmende  und  komple- 
mentaere  Eigenschaften  des  menschlichen  Serums,  Wien.  klin. 
Woch.,  1909,  265. 
Hecht,  Hugo: 

Eine  Vereinfachung  der  Komplementbindungsreaktion  bei  Syphilis, 

Wien.  klin.  Woch.,  1909,  338. 
Was  leistet  die  Serodiagnose  dem  praktischen  Arzte?  Prager  med. 

Woch.,  1910,  xxxv,  166. 
Zur  Technik  der  Seroreaktion   bei   Syphilis,  Ztschr.  f.    Immuni- 
tatsf.,  1910,  v,  572. 
Hecht,  V.,   Lateiner,  M.,   and  Wilenko,  M.:  Ueber  Komplementbin- 
dungsreaktion bei  Scharlach,  Wien.  klin.  Woch.,  1909,  p.  523. 
Heckmann:    Zur  Aetiologie  der    Arthritis    deformans,    Munch,    med. 

Woch.,  1909,  lvi,  1588. 
Hendel  and  Schultz:  Beitrage  zur  Frage  der  Komplementablenkenden 
Wirkung  der  Sera  von  Scharlachkranken,  Zeitschr.  f.  Immun., 
1908-09. 
Henkel:  Untersuchungen  ueber  die  Cerebrospinalfluessigkeit  bei  Geistes 

und  Nervenkranken,  Arch.  f.  Psy.,  1907,  327. 
Herxheimer:  Arsenobenzol  und  Syphihs,  Deut.  med.  Woch.,  1910,  1517. 
Herxheimer  and  Schoenfeld:  Weitere  Mitteilungen  ueber  die  Wirkung 
des  Ehrlichschen  Arsenobenzols  bei  Syphilis,  Med.  Klin.,  1910, 1400. 
Hess  and  Poetzl:  Ueber  Schwankungen  des  Zuckergehaltes  des  Liquor 
C.  R.  bei  psychischen  Erkrankungen,  Wien,  klin.  Woch.,  1910, 1065. 
Hoehne: 

Was  leistet  zur  Zeit  die  Wassermannsche  Reaktion  fuer  die  Praxis? 

Med.  Klin.,  1908,  1787. 
Ueber  das  Verhalten  des  Serums  von  Scharlachkranken  bei  der 
Wassermannschen  Reaktion  auf  Syphihs,  Berl.  klin.  Woch.,  1908, 
1488. 
Die  W.  R.  und  ihre  Beeiflussung  durch  die  Therapie,  Berl.  klin. 
Woch.,  1909,  869. 
Hoehne,  Fritz:  Ueber  die  verschiedenen  Modifikationen  der  W.  R., 

Berl.  klin.  Woch.,  1910,  334. 
Hoffmann  and  Blumenthal:  Die  Serodiagnostik  der  Syphilis  und  ihre 

Verwendbarkeit  in  der  Praxis,  Dermat.  Zeitschr.,  1908,  xv,  23. 
Hofmann:   Ueber   das   wahrscheinliche   Vorkommen   von   Carbamin- 

sausre  bei  Eklampsie,  Centralbl.  f.  inn.  Med.,  1897,  p.  725. 
Holm:  Der  Befund  der  Lumbalfluessigkeit  bei  tuberculoeser  Meningitis, 

Berl.  klin.  Woch.,  1911,  No.  18. 
Holzmann : 

Fortschritte  in  Bezug  auf  die  Diagnostik  der  syphilitischen  und 
metasyphilitischen  Erkrankungen  des  Zentralnervensystems  ver- 
mitttelst  der  vier  Reaktionen,  Die  Heilkunde,  Jahrgang,  1911. 


LITERATURE  293 

Holzmann : 

Liquor  C.  R.  und  W.  R.,  Neurol.  Centralbl.,  1912,  No.  2. 

Scharlach  und   Wassermannsche  Syphilisreaktion,   Miinch.   med. 
Woch.,  1909,  715. 
Hoppe:   Ueber   die   chemisette   Zusammensetzung   der   Cerebrospinal- 

fluessigkeit,  Virchow's  Arch.,  1859,  vol.  xvi,  p.  391. 
Huebner:  Zur  Lehre  von  den  syphilogenen  Erkrankungen  des  Zent- 

ralnervensystems,  Jahresvers.  des  deutsch.  Vereins  f.  Psy.,  April 

23  and  24,  1909;  ref.  in  Allgemeine  Zeits.  f.  Psy.,  vol.  lxvi,  pp.  657, 

658. 

FRENCH  LITERATURE 

Hallion  and  Bauer:  Sur  les  variations  du  glucose  C.  R.  dans  un  cas  de 

m^ningite  a  bacilles  de  Pfeiffer,  Rev.  Neurologique,  March  2,  1911. 
Haushalter  and  Thiry:   Etudes  sur  l'hydroc6phahe,  Revue  de  Med., 

Aug.  10,  1897. 
Hirschhorn:  Meningite  tuberculeuse;  valeur  de  l'examen  du  liquide  B. 

R.,  These  de  Paris,  No.  216,  1903. 
Hugot:  Un  cas  de  meningite  a  bacille  d'Eberth,  Gaz.  hebdomad.,  1899, 

No.  20. 
Hutinel:  Reactions  meningees  dans  les  ery themes   chez  les  enfants, 

Presse  med.,  March  24,  1909 


GERMAN  LITERATURE 

Isabolinsky:    Beitrage    zur   klinischen    Beurtheilung  der  Serumdiag- 
nostik  der  SyphiUs,  Arbeiten  aus  dem  Instit.  zur  Erforschung  der 
Infektionskrankheiten,  Bern,  1909. 
Iversen : 

Ueber  die  Wirkung  des  neuen  Arsenpraeparates  (606)  Ehrlich's  bei 

Rekurrens,  Miinch.  med.  Woch.,  1910,  777. 
Ueber  die  Behandlung  der  Syphilis  mit  dem  Praeparate   "606" 
Ehrlichs,  Ibid.,  1910,  1723. 

FRENCH    LITERATURE 
Iscovesco: 

Etudes  sur  les  constituants  colloidaux  des  humeurs  de  1'organisme; 

Liquide  C.  R.  normal,  C.  R.  de  la  Soc.  de  Biol.,  1907,  p.  183. 
Les  lipoides,  La  presse  m6d.,  1908,  Nos.  58,  67,  70. 

J 

ENGLISH  LITERATURE 

Jones: 

A  Simplified  Technic  for  Accurate  Cell  Enumeration  in  Lumbar 
Puncture,  Revue  of  Neurol,  and  Psych.,  1907,  p.  539. 


294      SEROLOGY  OF    NERVOUS    AND    MENTAL   DISEASES 

Jones : 

The  Protein  Content  of  Cerebrospinal  Fluid  in  General  Paralysis, 

Revue  of  Neurol,  and  Psych.,  June,  1909,  p.  379. 
Modern  Progress  in  Our  Knowledge  of  the  Pathology  of  General 

Paralysis,  Lancet,  1909,  p.  209. 
A  Review  of  our  Present  Knowledge  Concerning  the  Serodiagnosis 

of  General  Paralysis,  Amer.  Jour,  of  Insanity,  1909,  p.  653. 


GERMAN  LITERATURE. 

Jach:  Technik  und  Ergebnisse  der  Lumbalpunktion,  Arch.  f.  Psych. 
Jacobsthal: 

Ueber  positive  W.  R.  der  Lumbalfluessigkeit   bei  negativer  des 
Blutes,  Munch,  med.  Woch.,  1909,  p.  2662. 

Die  W.  R.  eine  Precipitationsreaktion,  Munch,  med.  Woch.,  1910, 
215. 

Zur  Frage  nach  der  Herkunft  der  die  W.  R.  herforrufenden  Sub- 
stanzen,  Ibid.,  1036. 
Jadassohn:    Bedeutung   der    modernen    Syphilisforschung,    besonders 

der  Serodiagnostik,  fuer  die  Klinik  der  Syphilis,  Korrespondenzbl. 

f.  Schweizer  Aerzte,  1909,  No.  5. 
Jaksch,  R.:  Ueber  die  Zusam m ensetzung  der  Cerebrospinalfluessigkeit, 

Klinische  Diagnostik  innerer  Krankheiten,  5th  edition,  p.  567. 
Jaworski  and  Lapinski:   Ueber  das  Schwinden  der  W.  R.  bei  syphilit- 

ischen  Erkrankungen  und  einige  strittige  Punkte  derselben,  Wien. 

klin.  Woch.,  1909,  1442. 
Jerusalem:  Ueber  ein  neues  Verfahren  der  Bestimmung  der  Milchsauere 

in  organen  und  Tierischen  Fluessigkeiten,  Biochemische  Zeitschr., 

1909,  p.  361. 
Jesionek  and  Meirowsky :  Die  praktische  Bedeutung  der  W.  R.,  Munch. 

med.  Woch.,  1909,  2297. 
Jochmann  and  Toepfer:  Zur  Frage  der  Spezifizitaet  der  Komplement- 

bindunsmethode  bei  Syphilis,    Munch,  med.  Woch.,   1908,  1690. 
Jolowicz:  Ueber  Behandlungsversuche  mit  Natrium  nucleinicum  und 

Salvarsan   bei   progessiver   Paralyse,    unter   besonderer  Berueck- 

sichtigung  der  Veraenderungen  des  Liquir  cerebrospinahs,  Neurol. 

Centralbl.,  1913,  No.  4. 
Jundell,  Almkvist,  and  Sandmann:  Wassermannsche  Syphilis  Reaktion 

bei  Lepra,  Centralbl.  f.  innere.  Med.,  1908,  1181. 
Junkermann:   Die   Behandlung   der   Syphihs  mit   Ehrhch-Hata  606, 

Med.  Klin.,  1910,  1350. 


FRENCH  LITERATURE 

Jacobaeus  and  Backmann:  Sur  les  differentes  modifications  de  la  reac- 
tion de  Wassermann.  C.  R.  Soc.  Biol.,  1909,  No.  30. 


LITERATURE  295 

Jaskowski  and  Rajchmann:  Quelques  remarques  sur  la  reaction  de 
Wassermann  dans  le  tabes  et  la  paralysie  generale,  C.  R.  de  la 
Soc.  de  Biol.,  66,  14,  618,  1909. 

Javorski:  Influence  du  traitement  mercuriel  sur  la  composition  du 
liquide  C.  R.  dans  le  maladies  du  systeme  nerveux  de  nature 
syphilitique  ou  parasyphilitique,  Revue  neurol.,   1910,  p.  264. 

Jeanselme  and  Sezary:  Lymphocytose  C.  R.  et  formule  sanguine  chez 
les  Syphilitiques,  Compt.  Rend,  de  la  Soc.  de  Biologie,  64,  5,  201. 

Joffroy  and  Mercier:  De  l'utilite  de  la  ponction  lombaire  pour  le  diag- 
nostic de  la  paralysie  generale,  Congres  des  m6d.  alienist,  Grenoble, 
1902,  12th  session. 

Joltrain:  Nouvelles  methodes  de  sero-diagnostic,  Paris,  1910. 

Jousset:  Les  serums  anti-tuberculeux.  Precipito-diagnostic  de  la  tuber- 
culose,  C.  R.  de  la  Soc.  Biol.,  Dec.  11,  1909. 

Jousset  and  Paraskevopoulos:  De  la  variabilite  du  complement  et  des 
causes  d'erreur  dans  le  syphilodiagnostic  par  la  reaction  de  fixa- 
tion, C.  R.  de  la  Soc.  de  Biol.,  lxvii,  22. 


ENGLISH  LITERATURE 

Kakels,  M.  S.:  Concerning  the  Ehrlich-Hata  Preparation  606,  Med. 

Rec,  1910,  1079. 
Kaliski,  D.  J.:  Specificity  of  the  Noguchi  Modification  of  the  Wasser- 
mann Reaction,  Arch,  of  Internal  Med.,  1910,  205. 
Kaplan,  D.  M.: 

The  Conservative  Utilization  of  the  Wassermann  Reaction,  Jour. 
Amer.  Med.  Assoc,  Dec.  3,  1910. 

The  Theoretical  Consideration  of  the  Wassermann  Reaction  and 
its  Practical  Application,  Amer.  Jour.  Med.  Sci.,  July,  1910. 

The  Principles  and  Technic  of  the  Wassermann  and  Noguchi 
Reactions  and  their  Comparative  Value  to  the  Clinician,  Amer. 
Jour.  Med.  Sci.,  January,  1910. 

The  Practical  Value  of  the  Wassermann  Test,  Med.  Rec,  June,  15, 
1912. 

Neurological  Serology,  Jour.  Nerv.  and  Mental  Dis.,  June,  1911. 

The  Laboratory  Findings  in  Neurological  Manifestations,  N.  Y. 
Med.  Jour.,  July  22,  1911. 

The  Wassermann  Test:  Some  Factors  of  Non-specific  Inhibition, 
N.  Y.  Med.  Jour.,  Sept.  7,  1912. 

Concerning  the  Restoration  of  Inhibitory  Qualities  in  Liver  Ex- 
tracts, Med.  Rec,  Nov.  19,  1912. 

Approximate  Estimation  of  Protein  (Globulin?)  in  the  Cerebro- 
spinal Fluid,  Med.  Rec,  Dec.  31,  1912. 

The  Wassermann  Fast  Tabes,  Jour.  Amer  Med.  Assoc,  Dec 
20,  1913. 


296      SEROLOGY   OF   NERVOUS    AND   MENTAL  DISEASES 

Kaplan,  D.  M.: 

A  Quantitative  Chemical  Reaction  for  the  Control  of  Positive 

Wassermann  Results,  N.  Y.  Med.  Jour.,  June  7,  1913. 
The    Laboratory    Differentiation    Between    General   Paresis   and 
Cerebrospinal  Syphilis  and  the  Serology  of  Spinal  Cord  Tumors, 
Amer.  Jour,  of  Insan.,  October,  1912. 
Amino  (NH2)  Nitrogen  Content  of  Syphilitic  and  Non-syphilitic 

Sera,  N.  Y.  Med.  Jour.,  July  26,  1913,  2d  communication. 
The   Importance   of   Serological   Analyses   in   Neurology,    N.   Y. 
Med.  Jour.,  Aug.,  16,  1913. 
Kaplan  and  Casamajor,  L. :  The  Neuroserological  Findings  in  Tabes, 
Cerebrospinal  Syphilis,   General  Paresis,    and  Other  Nervous  and 
Mental  Diseases,  Archives  of  Internal  Med.,  Feb.,  1912. 
Kaplan  and  McClelland: 

A  Quantitative  Chemical  Reaction  for  the  Control  of  Positive 

Wassermann  Reactions,  Nov.  22,  1913,  3d  communication. 
The  Precipitation  of  Colloidal  Gold,  Jour.   Amer.  Med.  Assoc, 
Feb.  14,  1914. 
Karpas,  M.: 

Clinical  Significance  of  the  Cerebrospinal  Fluid  in  Nervous  and 

Mental  Diseases,  Jour.  Amer.  Med.  Assoc,  July  26,  1913. 
The  Significance  of  the  Wassermann  Reaction  for  Psychiatry, 

Bellevue  Hosp.  Bull.,  N.  Y.,  1911. 
The  Clinical  Interpretations  of  the  Serological   Content  of  the 
Blood  and  Cerebrospinal  Fluid,  with  Some  Reference  to  the 
Cytology  and  Chemistry  of  the  Latter  in  Mental  Diseases,  Amer. 
Jour,  of  Insan.,  1912,  vol.  lxix. 
Kensington:  On  Rhythmical  Variations  in  the  Cerebrospinal  Pressure, 

Brit.  Med.  Jour.,  1908,  553. 
Klein,  Bernhard:  The  Practice  of  the  Wassermann  Reaction  from  the 

Quantitative  Standpoint,  Lancet,  1910,  1255. 
Koplik,  H.:  Meningitis  of  the  Epidemic  Type  in  Children  Below  Two 

Years  of  Age,  Jour.  Amer.  Med.  Assoc,  June  17,  1913. 
Kramer: 

The  Circulation  of  the  Cerebrospinal  Fluid  and  its  Bearing  on  the 
Pathogenesis  of  Poliomyelitic  Disease,  N.  Y.  Med.  Jour.,  1912, 
1532. 
Cerebrospinal  Fluid  in  General  Paresis,  Amer.  Jour,  of  Insan., 
1903-04. 

GERMAN  LITERATURE 

Kaemmerer,  Hugo:  Diagnostische  Intrakutanreaktion  mit  Spirochae- 

tenextrakt,  Munch,  med.  Woch.,  1912,  1534. 
Kafka: 

Ueber  die  klinische  Bedeutung  der  Komplementbindungsreaktion 
im  Liquor  cerebrospinalis,  speciell  bei  der  progressiven  Paralyse, 
Monatschr.  f.  Psych,  u.  Neurol.,  1909,  vol.  xxiv. 


LITERATURE  297 

Kafka: 

Ueber  Technik  und  Bedeutung  der  cytologischen  Untersuchung 
des  Liquor  cerebrospinalis,  Monatschr.  f.  Psych,  u.  Neurol., 
1910,  vol.  xxvii. 

Zur  Frage  der  Permeabilitaet  der  Meningen,  Med.  Klin.,  1910,  5,  2. 

Ueber  die  Polynucleose  im  Liquor  cerebrospinalis  bei  der  pro- 
gressiven  Paralyse,  Zeitschr.  f.  d.  ges.  Neurol,  u.  Psych.,  1910, 
648. 

Beitrage  zur  Pathologie  des  Liquor  cerebrospinalis,  Zeitschr.  f. 
d.  ges.  Neurol,  u.  Psych.,  1910,  117. 

Ueber  cytolyse  im  Liquor  cerebrospinalis,  Ibid.,  1911,  252. 

Ueber  die  Bedingungen  und  die  praktische  und  theoretische 
Bedeutung  des  Vorkommens  Hammelblutloesender  Normalam- 
boceptoren  und  des  Komplements  im  Liquor  cerebrospinalis, 
Zeitschr.  f.  d.  ges.  Neurol,  u.  Psych.,  1912,  vol.  ix. 

Ueber  die  Fermente  des  Liquor  cerebrospinalis,  Neurol.  Centralb., 
1912,  No.  10. 

Zur  Biologie  des  Liquor  cerebrospinalis;  Ueber  die  Fermente  des 
Liquor  C.  S.  mit  besonderer  Beruecksichtigung  der  Psychosen, 
Mittheilungen  aus  den  Hamburger  Staatskrankenanstalten, 
1912,  47. 

Ueber  Entstehung,   Circulation  und  Funktion  des  Liquor  cere- 
brospinalis, Vortrag  gehalten  bei  Jahresversammlung  des  deut- 
chen  Vereins  f.  Psychiatrie  zu  Kiel,  May  30,  1912. 
Kalb,  Richard:  Ueber  die  Einwirkung  des  Ehrlichschen  Arsenobenzols 

auf  die  Lues  der  Kinder  mit  besonderer  Beruecksichtigung  der 

Syphilis  congenita,  Wien.  klin.  Woch.,  1910,  1378. 
Kaplan,  D.  M.:  Analyse  der  Spinalfluessigkeit  und  des  Blutserums  in 

ihrer  Bedeutung  fuer  die  Neurologic,  Deut.  med.  Woch.,  1913, 

No.  22. 
Kauff  mann : 

Das  Cholin  des  Liquor  cerebrospinalis,  Neurol.  Centralbl.,  1908,  6, 
p.  260.      Answer  to  Donath,  Ibid.,  1908,  No.  20. 

Ueber  das  Vorkommen  von   Cholin   in   pathologischer  Lumbal- 
fluessigkeit,  Zeitschr.  f.  phys.  Chem.,  June,  1910,  p.  343. 
Kauff  mann  and  Vorlaender:  Ueber  Nachweis  des  Cholins,  Dissert., 

HaUe,  1909. 
Kellner,  Clemenz,  Brueckner,  and  Rautenberg:  W.  R.  bei  Idiotie,  Deut. 

med.  Woch.,  1909,  No.  42. 
Kiralfy,  Geza:  Zur  Frage  des  Zusammenhanges  zwischen  W.  R.  und 

Antiluetischer  Behandlung,  Wien.  klin.  Woch.,  1910,  xxiii,  162. 
Kiss,  J.:  Experimentelle  Beitrage  zur  Erklaerung  der  W.  R.,  Zeitschr. 

f.  Immunitaetsf.,  1909,  vol.  iv. 
Klausner,  E.: 

Vorlaufige  Mitteilung  ueber  eine  Methode  der  Serodiagnostik  bei 
Lues,  Wien.  klin.  Woch.,  1908,  xxi,  p.  214. 

Ueber  eine  Methode  der  Serodiagnostik  bei  Lues,  Ibid.,  p.  363. 


298      SEROLOGY    OP   NERVOUS    AND    MENTAL    DISEASES 

Klausner,  E.:  Klinische  Erfahrungen  ueber  das  Praecipitationsphaeno- 
men  mit  destillirtem  Wasser  im  Serum  Syphilitischer,  Wien.  klin. 
Woch.,  p.  940. 
EQeischmidt : 

Ueber   die   Sternsche   Modifikation    der   W.    R.,    Zeitschrift    fiir 

Immunitaetsforschung,  1909,  p.  512. 
Bildung  Komplementbindender  Antikoerper  durch  Lipoidkoerper, 
Berl.  klin.  Woch.,  1909,  57. 
Klieneberger: 

Zur    Erweiterung    der    Wassermannschen    Methode,    Monatschr. 

fiir  Psychiatrie,  1912,  vol.  xxxii,  p.  76. 
Ein    eigenthuemlicher    Liquorbefund    bei    Rueckenmarkstumoren 
(Xanthochromic,     Fibringerinnung,    und    Zellvermehrung    der 
cerebrospinalfiuessigkeit),    Monatschr.    f.    Psych,    u.    Neurol., 

1910,  vol.  xxviii. 

Zur    differentialdiagnostischen    Bedeutung   der    Lumbalpunktion 
und  der  serodiagnostik,  Arch.  f.  Psych,  u.  Nervenkr an kh eiten, 

1911,  vol.  xlviii. 
Knopf elmacher  and  Lehndorff: 

Komplementablenkung  bei  Muettern  hereditaer  luetischer  Saueg- 

linge,  Wien.  med.  Woch.,  1908,  p.  813. 
Komplementfixation    bei    Muettern   heredo-syphilitischer    Saueg- 

linge  (Zweite  Mitteilung),  Med.  Klin.,  1908,  1182. 
Hydrocephalus    chronicus    internus  congenitus   und   Lues,  Ibid., 

1908,  1863. 
Die  Untersuchungen  heredo-luetischer  Kinder  Mittels  der  W.  R., 

Wien.  med.  Woch.,  1909,  2230. 
Das  CoUe'sche  Gesetz,  Med.  Klin.,  1909,  1506. 
Das  Colle'sche  Gesetz  und  die  neuen  Syphilisforschungen,  Jahr- 

buch  f.  Kinderheilk.,  1910,  156. 
Koenig:  Warum  ist  die  Hecht'sche  Modifikation  der  Wassermannschen 
Lues-reaktion  dieser  und  der  Stern'schen  Modifikation  vorzuzienen? 
Wien.  klin.  Woch.,  1909,  1127. 
Kopp,  C: 

Ueber  die  Bedeutung  der  W.  R.  Serodiagnose  der  Sj^philis  fuer  die 

Praxis,  Munch,  med.  Woch.,  1909,  1184.  ' 
Zur   Frage   der   praktischen    Bedeutung   der    Sero-diagnose   der 

Syphilis,  Munch,  med.  Woch.,  1910,  1126. 
Krefting: 

Leichensera   und    die    Wassermannsche    Syphilisreaktion,    Deut. 

med.  Woch.,  1910,  356. 
Aorteninsiffizience  und  die  Wassermannsche  Luesreaktion,  Berl. 

klin.  Woch.,  1910,  713. 
Kretschmer :  Lymphocytose  des  Liquor  cerebrospinalis  bei  Lues  heredi- 
taria tarda,  Deut.  med.  Woch.,  1907,  No.  46. 
Kroenig : 

Ueber  Lumbalpunktion   bei  Eklampsie,  Centralb.   f.    Gynaekol., 

1904,  1153. 


LITERATURE  299 

Kroenig:  Ueber  die  diagnostische  Bedeutung  gewisser  bistologischer  und 

physikalischer  durch  die  Lumbalpunktion  gewonnener   Befunde, 

Ref.  in  Wien.  med.  Blaetter,  1899,  vol.  xxv. 
Kromayer:  Theoretische  und  praktische  Erwaegungen  ueber  Ehrlich- 

Hata  606,  Berl.  klin.  Woch.,  1910,  1585. 
Kroner:  Wassermannsche  Serodiagnostik  bei  Lues,  Berl.  klin.  Woch., 

1908,  149. 
Kronf eld,  A. :  Beitrage  zum  Studium  der  W.  R.  und  ihre  diagnostischen 

Anwendung  in  der  Psychiatrie,  Zeitschr.  f.  d.  Ges.   Neurol,  u. 

Psych.,  1910,  376. 
Kutner:  Ueber  den  diagnostischen  Wert  der  Lumbalpunktion  in  der 

Psychiatrie,  Monatschr.  f.  Psych,  u.  Neurol.,  1906,  p.  540. 

L 
ENGLISH  LITERATURE 

Litterer:   Serodiagnosis  of  Syphilis,  Jour.  Amer.   Med.  Assoc,   1909, 

1537. 
Livingood:  Epidemic  Cerebrospinal  Meningitis,  Bull.  Johns  Hopkins 

Hosp.,  No.  273. 
Louria,   Leon:   The   Diagnostic   and   Therapeutic   Value   of  Lumbar 

Puncture,  Med.  Rec,  Nov.  12,  1912. 

GERMAN  LITERATURE 

Landau  and  Halpern:  Beitrage  zur  Chemie  der  Cerebrospinalfluessig- 

keit,  Biochem.  Zeitschr.,  1908,  No.  9. 
Landsteiner  and  Mueller:  Zur  Frage  der  Komplementbindungsreak- 

tionen  bei  Syphilis,  Munch,  klin.  Woch.,  1907,  No.  50,  p.  1565. 
Landsteiner  and  Stankoviz :  Ueber  die  Bindung  von  Komplement  durch 

suspendierte  und  kolloid-geloeste  Substancen,  Centralb.  f.  Bakt., 

Orig.  I.,  1906,  Heft  4. 
Landsteiner,  Mueller,  and  Poetzl :  Zur  Frage  der  Komplementbindungs- 

reaktion  bei  Syphilis,  Wien.  klin.  Woch.,  1907,  1565. 
Lange,  Carl: 

Ergebnisse  der  W.  R.  bei  Vorbehandlung  der  Sera  mit  Barium- 
sulphate  nach  Wechselmann,  Deut.  med.  Woch.,  1910,  217. 

Zur  Kenntniss  der  W.  R.  insbesondere  bei  mit  Ehrlichs  606  be- 
handelten  Luesfaellen,  Berl.  klin.  Woch.,  1910,  656. 

Die  Ausflokkung  kolloidalen  Goldes  durch  Cerebrospinalfluessig- 
keit  bei  syphilitischen  Affectionen  des  Centralnervensystems, 
Zeitschr.  f.  Chemotherapie,  1912,  No.  1. 
Langstein:  Zur  Kenntnis  der  Cerebrospinalfluessigkeit  in  einem  Fall 

chronischer  Hydrocephalic,  Jahrb.  f.  Kinderheilk.,  1903,  p.  924. 
Lateiner:  Das  Verhalten  des  Reduxionsindex  nach  E.  Mayerhofer  in 

der  normalen  und  pathologischen  Cerebrospinalfluessigkeit,  Wien. 

klin.  Woch.,  1911,  No.  22. 


300      SEROLOGY    OF   NERVOUS   AND    MENTAL   DISEASES 

Ledermann: 

Ueber   den   praktischen  Wert    der    Serodiagnostik  der   Syphilis, 

Deut.  med.  Woch.,  1908,  p.  1760. 
Ueber  Beziehungen  der  Syphilis  zu  Nerven  und  anderen  inneren 
Erkrankungen  auf  Grund  von  573  serologischen  Untersuchungen, 
Berl.  Idin.  Woch.,  1910,  1787. 
Ledermann  and  Reinhold :  Ueber  die  Bedeutung  der  Wassermannschen 
Serumreaktion  fuer  die  Diagnostik  und  Behandlung  der  Syphihs, 
Med.  klin.,  1909,  419. 
Leede:   Bakteriologische   Untersuchungen   des   Liquor   cerebrospinalis 

bei  Diphtherie,  Zeitschr.  f.  Hygiene,  1911,  p.  79. 
Lehndorf  and  Baumgarten:  Zur  Chemie  der  Cerebrospinalfluessigkeit, 

Zeitschr.  f.  experim.  Pathol,  u.  Ther.,  1907,  p.  330. 
Lenhartz : 

Ueber  den   diagnostischen  und  therapeutischen  Wert  der  Lum- 

balpunktion,  Munch,  med.  Woch.,  1896,  Nos.  8,  9. 
Weitere  Erfahrungen  mit  der  Lumbalpunktion,  Therapeut.  Monat., 
98,  437. 
Lesser,  Fritz: 

Tabes  und   Paralyse  im  Lichte  der  neueren   Syphilisforschung, 

Berl.  klin.  Woch.,  1908,  No.  39. 
Zu  welchen  Schluessen  berechtigt  die  W.  R.?  Med.  klin.,  1908,  299. 
Weitere  Ergebnisse  der  Serodiagnostik  der  Syphihs,  Deut.  med. 

Woch.,  1909,  379. 
Zur  Technik  und  zum  Wesen  der  W.  R.,  Berl.  klin.  Woch.,  1909, 

974. 
Die  verschiedenen  Modifikationen  der  W.  R.  und  ihre  Bewertung, 
Dermat.  Zeitschr,,  1910,  504. 
Lewandowsky:  Zur  Lehre  von  der  Cerebrospinalfluessigkeit,  Zeitschr. 

f.  klin.  Med.,  1900,  No.  40,  p.  480. 
Lewkowicz :  Zur  Aetiologie  der  Cerebrospinalmeningitis  und  zur  Bedeu- 
tung der  Lumbalpunktion,  Przglad  lekarski,  1900,  48-52. 
Liebscher:  Die  cytologische  und  chemische  Untersuchungen  des  Liquor 
cerebrospinalis  bei  Geisteskranken,   insbesonderheit  bei  progres- 
siver  Paralyse,  Wien.  med.  Woch.,  1906,  2209. 
Liefmann:  Ueber  den  Mechanismus  der  Seroreaktion  der  Lues,  Munch. 

med.  Woch.,  1909,  2097. 
Lippmann,  H. : 

Ueber  die  Beziehungen  der  Idiotie  zur  Syphihs,  Deut.  Zeitschr.  f. 

Nervenheilk.,  1910,  81. 
Ueber  den  Zusammenhang  von  Idiotie  und  Syphihs,  Munch,  med. 
Woch.,  1909,  No.  47,  p.  2417. 
Lockemann:   Nachweis   von   Fleischmilchsauere   im   Blut,  Urin,  und 

Cerebrospinalfluessigkeit,  Munch,  med.  Woch.,  1906,  No.  7. 
Loehlein,  M.: 

Die  Luesreaktion  an  der  Leiche,  Vortschritte  der  Med.,   1909, 
No.  3. 


LITERATURE  301 

Loehlein,  M.: 

Zur   Frage   der   Verwertbarkeit   der   Wassermannschen   Syphilis- 

reaktion  an  der  Leiche,  Folia  Sero.,  1910,  227 
Ueber  die  Seroreaktion  auf  Syphilis  nach  Wassermann,  Fortschr. 
der  Med.,  1909,  vol.  xxvii,  p.  97. 

FRENCH  LITERATURE 

Labuze:   Des  reactions  meningees  dans   les  polynevrites,    These   de 

Montpellier,  No.  113. 
Laignel,  Lavastine,  and  Lasausse:  Sur  1' analyse  chimique  du  liquide  C. 

R.  des  paralytiques  genereaux,  Compt.  rend,  de  la  Soc.  de  Biol., 

1910,  vol.  lxviii. 
Lair:  Meningite  cerebro-spinale;  Diagnostic  et  Pronostic,  These  de 

Paris,  No.  546. 
Landowski  and  Claret :  Polynucleose  rachidienne  dans  3  cas  de  meningite 

tuber culeuse,  Archives  generates  de  Medicine,  Aug.,  1907,  p.  584; 

Progres  med.,  1908,  p.  245. 
Lannois,  Lesieur,  and  Gauthier:  Action  du  liquide  C.  R.  sur  quelques 

bacteries  pathogenes,  C.  R.  de  la  Soc.  de  Biol.,  July,  1908,  vol.  lxv. 
Lapersonne:  Lymphocytose  rachidienne  et  affections  oculaires,  Arch. 

d'ophthalmol.,  1903,  p.  337. 
Laruelle: 

Pression  rachidienne,  Ier.  Congres  beige  de  Neurologie  Liege,  1905. 

Ponction  lombaire  et  cytodiagnostic.     Importance  de  la  numera- 
tion, Jour,  de  Neurol.,  1906,  p.  576. 
Lassaigne:  Note  sur  la  composition  du  liquide  qui  se  trouve  dans  le 

canal  rachidien,  Annates  de  chimie  et  de  physique,   1826;  Jour. 

de  chimie  med.,  vol.  iv,  1828. 
Laubry  and  Paru:  La  reaction  de  Wassermann  au  cours  de  quelquse 

affections  cardio-vasculaires,  C.  R.  de  la  Soc.  de  Biol.,  1909,  lxvii, 

p.  48. 
Launois  and  Boulud:  Sur  la  teneur  en  sucre  du  liquide  C.  R.,  Rev. 

Neurol.,  May,  1904. 
Launois  and  Leroux:  Impermeabilite  meningee  au  mercure,  au  cours  du 

traitement  hydrargyrique  prolonge,  C.  R.  de  la  Soc.  de  Biol.,  1902, 

vol.  lxiv,  p.  1482. 
Laval:  Meningite  typhique,  These  de  Paris,  1903. 
Legry  and  Duvoir:  Reaction  meningee  au  cours  de  2  cas  d'intoxication 

par  l'oxyde  de  carbone,  Soc.  med.  des  Hop.,  Dec.  18,  1908. 
Leitao  d'Acunha  and  Vianna:  Contribution  a  la  cytologie  du  liquide 

C.  R.  dans  les  affections  nerveux  et  mentales,  Ann.  med.  Psychol., 

1909,  39. 
Lepine,  J.: 

Le  liquide  C.  R.  dans  le  processus  meninges  subaigues  d'origine 
rheumatismale,  Lyon  med.,  Aug.  23,  1903. 

A  propos  de  la  meningite  spinale  du  tabes,  Lyon  med.,  1905,  p.  981. 

Existe-il  une  meningite  urSmique?  Sem.  med.,  July  31,  1908. 


302      SEROLOGY   OF   NERVOUS    AND    MENTAL   DISEASES 

Leri: 

Sur  le  liquide  C.  R.  et  specialement  la  permeabilite  des  meninges 
dans  la  meningite  tuberculeuse,  Arch,  de  Med.  des  Enfants, 
1902,  vol.  vi,  p.  449. 
Etude  cytologique  et  cryoscopique.  Permeabilite  dans  les  men- 
ingites,  C.  R.  de  la  Soc.  de  Biol.,  July,  1901. 

Lesieur:  Cytologie  et  virulence  du  liquide  C.  R.  chez  les  rabiques, 
C.  R.  de  la  Soc.  de  Biol.,  vol.  lvii,  p.  615. 

Letulle,  Lagane,  and  Vincent :  Precipito-diagnostic  de  la  meningite  cere- 
bro-spinale,  C.  R.  de  la  Soc.  de  Biol,  May  15,  1909,  p.  758. 

Levaditi  and  Marie:  Action  de  liquide  C.  R.  de  paralytiques  genereaux 
sur  le  virus  syphilitiques,  C.  R.  de  la  Soc.  de  Biol.,  May,  1907; 
Sem.  med.,  1907,  No.  21. 

Levaditi  and  Yamanouchi: 

La  serodiagnostic  de  la  syphilis,  C.  R.  de  la  Soc.  de  Biol.,  1907, 

vol.  lxiii,  740. 
Diagnostic  de  la  syphilis  et  de  la  paralysie  generale,  C.  R.  de  la 
Soc.  de  Biol.,  1908,  Ixiv,  27,  349. 

Levaditi,  Laroche,  and  Yamanouchi :  Le  diagnostic  precoce  de  la  syph- 
ilis par  la  methode  de  Wassermann,  C.  R.  de  la  Soc.  de  Biol.,  1908, 
745. 

Levaditi,  Ravaut,  and  Yamanouchi:  Localisation  nerveuse  de  la  syph- 
ilis et  proprietes  du  liquide  C.  R.,  C.  R.  de  la  Soc.  de  Biol.,  1908, 
vol.  Ixiv. 

Loederich:  Leucocytose  C.  R.  tardive  dans  un  cas  de  meningite  tuber- 
culeuse, Gaz.  des.  Hop.,  1908,  897. 

Lutier:  Le  nouveaux  precedes  d'investigations  dans  le  diagnostic  de 
meningite  tuberculeuse,  These  de  Paris,  July  16,  1903. 


M 
ENGLISH  LITERATURE 

MacCambpell:  Studies  On  the  Clinical  Diagnosis  of  General  Paralysis 

of  the  Insane,  Jour.  Med.  Research,  1910,  No.  20. 
McDonagh,  J.  E.  R.: 

Wassermann' s  Reaction  from  a  Practical  Point  of  View,  Lancet, 
1910,  920. 

Salvarsan  in  Syphilis  and  Allied  Diseases,  Oxford  Med.  Publica- 
tions, London,  1912. 
Mcintosh:  The  Serodiagnosis  of  Syphilis,  Lancet,  1909,  p.  1515. 
M'Intosh,  J. :  Observations  on  the  Wassermann  Reaction,  with  Special 

Reference  to  the  Influence  of  Specific  Treatment  Upon  It,  Zeitschr. 

f.  Immunitaets.,  1910,  p.  76. 
M'Kenzie:  The  Serum  Diagnosis  of  Syphilis,  Jour.  Path,  and  Bact., 

1909,  311. 


LITERATURE  303 

Morse:  The  Value  of  Lumbar  Puncture  and  of  the  Leukocyte  Count 
in  the  Diagnos  isof  Acute  Poliomyelitis  (Infantile  Paralysis),  Arch, 
of  Pediat.,  1911,  No.  28,  p.  164. 
Morton:  Biochemical  Examination  of  the  Cerebrospinal  Fluid  in  Cases 

of  Mental  Disease,  Jour,  of  Mental  Sci.,  1911,  vol.  lvii. 
Mott: 

Oliver-Sharpey  Lectures  on  the  Cerebrospinal  Fluid,  Lancet,  1910, 

p.  179,  No.  2. 
The  Cerebrospinal  Fluid,  Lancet,  July  2  and  9,  1904. 
The  Morrison  Lectures  on  the  Pathology  of  Syphilis  of  the  Nervous 
System  in  the  Light  of  Modern  Research,  Arch,  of  Neurol,  and 
Psych.,  1909,  vol.  iv. 
A  Lecture  on  the  Cerebrospinal  Fluid  in  Relation  to  Diseases  of 

the  Nervous  System,  Brit.  Med.  Jour.,  1904. 
The  Diagnosis  of  Syphihtic  Diseases  of  the  Nervous  System,  Brit. 
Med.  Jour.,  1909,  p.  1403. 
Mott  and  Halliburton: 

On  the  Physiological  Action  of  Cholin  and  Neurin,  Philosophical 

Trans,  of  the  Royal  Soc.  of  London,  1899,  vol.  cxci. 
The  Chemistry  of  Nerve  Degeneration,  Lancet,  April  13,  1901. 
Muir,  R. :  Studies  on  Immunity,  London,  1909. 
Muirhead : 

The  Occurrence  of  Organisms  in  the  Blood  and  the  Cerebrospinal 

Fluid  in  Mental  Diseases,  Jour.  Ment.  Sci.,  1910,  232. 
The  Wassermann  Reaction  in  the  Blood  and  Cerebrospinal  Fluid 
and  the  Examination  of  Cerebrospinal  Fluid  in  General  Paralysis 
and  Other  Forms  of  Insanity,  Jour.  Ment.  Sci.,  1910,  649. 
The  Wassermann  Reaction  in  the  Blood  and  Cerebrospinal  Fluid 
in  Insanity  and  Examination  of  the  Spinal  Fluid,  Lancet,  1911, 
515. 
Myers:  Cerebrospinal  Fluid  in  Certain  Forms  of  Insanity  with  Special 
References  to  the  Potassium  Content,  Jour,  of  Biol.  Chem.,  Balti- 
more, May,  1909. 


GERMAN  LITERATURE 

Mansfeld,  G. :  Ueber  den  Donatschen  Nachweis  von  Cholin  in  Faellen 

von  Epilepsie,  Hoppe-Seyler,  Zeitschr.  f.  phys.  Chem.,  1904,  vol.  xlii. 
Margulies :  Ueber  die  Aktivitaet  des  Liquor  cerebrospinalis,  Monatschr. 

f.  Psych,  und  Neurol.,  1912,  No.  31. 
Marschalko,  Janco,  and  Csiki:  Der  klinische  Wert  der  Wassermannschen 

Syphilisreaktion,  Arch.  f.  Dermat.  und  Syphil.,  1910,  vol.  ci. 
Maslakowich  and  Liebermann: 

Theorie  und  Technik  der  Reaktion  von  Wassermann  imd  die 
diagnostische  Bedeutung  derselben,  Zentralb.  f.  Bakt.,  1908,  378. 

Zur  Technik  der  W.  R.,  Zeitschr.  f.  Immunitaetsf.,  1909,  564. 


304      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

Mayerhofer: 

Zur  Charakteristik  und  Differentialdiagnose  des  Liquor  cerebro- 
spinahs, Wien.  klin.  Woch.,  1910,  p.  651. 
Kritische  Bemerkungen  zur  Arbeit  von  G.  Simon  ueber  meine 

Methode  der  Permanganattitration  des  Liquor  cerebrospinal, 

Wien  klin.  Woch.,:  1911. 
Mayerhofer  and  Neubauer:  Ueber  Meningitis  tuberculosa  und  Meningi- 
tis serosa,  Ergebnisse  der  Permanganattitration  des  Liquor  cere- 
brospinalis,  Zeitschr.  f.  Kinderheilk.,  1912,  vol.  iii. 
Medizinische  Klinik:  Umfrage  ueber  die  Wirkung  des  Ehrlichschen 
Arsenobenzols  bei  Syphilis,  1910,   1451,  1500,  1533,  1573,  1614, 
1702,  1782. 
Meier,  George: 

Technik  und  klinische  Bedeutung  der  W.  R.  auf  Syphilis,  Berl. 

klin.  Woch.,  1907,  1636. 
Scharlach    und    Serodiagnostik    auf    Syphilis,    Med.    klin.,    1908, 

1383. 
Serologische  Untersuchungen  bei  Lepra,   Mitteilungen  und  Ver- 

handlungen   der   zweiten   Internat.    wissenschafthchen    Lepra- 

konferenz,  1909,  334. 
Ueber    Komplementbindung    mit    besonderer    Beruecksichtigung 

ihrer  praktischen  Anwendung  (zweiter  Teil),  Weichardt's  Jahres- 

bericht  ueber  die  Ergebnisse  der  Im m unit aetsf orschung,    1909, 

Abt.  i,  140-272. 
Meirowsky: 

Ueber  die  von  Bauer  vorgeschlagene  Technik  der  Wassermann- 

Neisser-Bruckschen  Reaktion,  Berl.  klin.  Woch.,  1909,  152. 
Ueber  die  von  M.  Stern  vorgeschlagene  Modifikation  der  W.  N.  B. 

Reaktion,  Berl.  klin.  Woch.,  1909,  1310. 
Ueber  paradoxe  Erscheinungen  bei  der  W.  R.,  Med.  klin.,  1910, 

947. 
Die  Einwirkung  des  Ehrlichschen  Mittels  auf  den  syphilitischen 

Prozess,  Ibid.,  1910,  1653. 
Merzbacher: 

Ergebnisse  der  Untersuchung  des  Liquor  cerebrospinalis,  Neurol. 

CentralbL,  1903,  548. 
Die  Beziehung  der  Syphihs  zur  Lymphocytose  der  Cerebrospinal- 

fluessigkeit  und  zur  Lehre  von  der  meningitischen  Reizung,  Cen- 

tralblatt  fur  Neurologie,  No.  212,  1906. 
Meyer,  E.: 

Utersuchungen  des  Liquor  cerebrospinahs  bei  Geistes  und  Nerven- 

kranken,  Arch.  f.  Psych.,  1907,  p.  971. 
Zur  Untersuchung  des  Liquor  cerebrospinahs,   Neur.   Centralb., 

1909,  402. 
Meyer,  L. :  Einige  Beitrage  zur  Theorie  und  Technik  der  W.  R.  und  zur 
Wertbemessung  der  geprueften  Seren,  Berl.  klin.  Woch.,   1909, 
829. 


LITERATURE  305 

Michaelis,  L.: 

Die  Wassermannsche  Syphilisreaktion,  Berl.  klin.  Woch.,  1907, 
1103. 

110  Faelle  von  Syphilis,  behandelt  nach  Ehrlich-Hata,  Berl.  klin. 
Woch.,  1910,  1195. 
Michaelis  and  Lesser:  Erfahrungen  mit  der  Serodiagnostik  der  Syphilis, 

Berl.  klin.  Woch.,  1908,  301. 
Mohr:  Zur  Pathologie  des  Liquor  cerebrospinalis,  Deut.  Zeitschr.  f. 

Nervenheilk.,  1912,  p.  417. 
Morgenroth    and    Stertz:    Ueber    den    Nachweis    syphihtischer    Anti- 

koerper  im  Liquor    cerebrospinahs  von  Paralytikern    nach    dem 

Wassermann   Plautschen   Verfahren   der    Komplementablenkung, 

Virch.  Arch.  f.  path.  Anat.,  1907,  vol.  clxxxvii,  p.  166. 
Much: 

Eine  Studie  ueber  sogenannte  Komplementbindungsreaktion, 
mit  besonderer  Beruecksichtigung  der  Lues,  Med.  klin.,  1908, 
1067,  1117. 

Nachpruefungen  der  Resultate  der  W.  R.,  Deut.  med.  Woch., 
1909,  606. 

Die  praktische  Brauchbarkeit  der  W.  R.,  Munch,  med.  Woch.,  1909. 

Psychiatrie  und  Serologic,  Berl.  klin.  Woch.,  1910,  1492. 
Much  and  Eichelberg:  Die  Komplementbindung  mit  waessrigem  Lues- 

extrakt  bei  nichtsyphilitischen  Krankheiten,  Med.  klin.,  1908,  671. 
Muehlens,  P.:  Ueber  Zuechtungsversuche  der  Spirochaeta  pallida  und 

Sp.  refringens,   sowie  Tierversuche  mit  den  kultivierten  Spiro- 

chaeten,  Klin.  Jahrbuch,  1910,  339. 
Muehsam:  Klinische  Leistungsfaehigkeit  der  Serodiagnostik  bei  Lues, 

Berl.  klin.  Woch.,  1908,  xlv. 
Mueller,  R.:  Zur  Verwertbarkeit  und  Bedeutung  der  Komplement- 
bindungsreaktion fuer  die  Diagnose  der  Syphilis,  Wien.  klin.  Woch., 

1908,  382. 
Muelzer,  P.: 

Praktische  Anleitung  zur  Syphilisdiagnose  auf  biologischem  Wege 
(Spirochaetennachweis,  W.  R.),  Berhn,  J.  Springer,  1910. 

Zur  Technik  und  praktischen  Verwertung  der  W.  R.,  Zeitschr.  f. 
Immunitaetsf.,  1910,  236. 
Muelzer  and  Michaelis:  Hereditaere  Lues  und  W.  R.,  Berl.  khn.  Woch., 

1910,  1402. 
Muir,  R. :  Ueber  die  Hitzbestaendigkeit  der  Blutkoerperchenreceptoren, 

Biochem.  Zeitschr.,  1909,  p.  510. 

FRENCH  LITERATURE 

Magendie : 

Memoire  sur  un  liquide  qui  se  trouve  dans  le  crane  et  la  colonne 
vert^brale  de  1'homme  et  des  animaux  mammiferes,  C.  R.  Acad, 
des  Sci.,  Jan.  10,  1825;  2  e  m6moire  in  Jour,  de  physiol.  experim. 
et  pathol.,  Jan.,  1827. 
20 


306      SEROLOGY    OF   NERVOUS    AND    MENTAL  DISEASES 

Magendie:  Recherches   physiologiques    sur   le    liquide    C.    R.,  Paris, 

1842. 
Maillard:  De  la  valeur  clinique  du  cytodiagnostic  C.  R.  dans  les  cas 

douteux  de  la  paralyse  generate  progressive,  These  de  Bordeaux, 

1901. 
Maillet:  Les  formes  frustes  et  larvees  des  meningites  cerebrospinales 

aigues,  les  reactions  meningees,  These  de  Montpellier,  Feb.  19, 

1910. 
Mancini:  Pouvoir  mydriatique  du  hquide  C.  R.  dans  un  cas  d'uremie 

aigue,  Revista  critica  clinica  med.,  vol.  x,  p.  387. 
Manicatide:  Diagnostic  bacteriologique  de  la  meningite  tuberculeuse, 

C.  R.  de  la  Soc.  de  Biol.,  1903,  p.  523. 
Marchand,  L:  Dosage  d'albumine  dans  quelques  maladies  mentalea 

et  specialement  la  Paral.  gen.,  Rev.  de  Psych,  et  de  Pathol.  Exper., 

1903,  p.  196. 
Margarot:  Zona  et  Meningite,  These  de  MontpeUier,  1910,  No.  102. 
Marie,  A. :  Du  serodiagnostic  en  psychiatrie,  Rev.  de  psych.,  Oct.,  1908. 
Marie  and  Crouzon:  Quelque  resultate  du  cytodiagnostic  du  liquide 

C.  R.,  Revue  Neurol.,  1903,  339. 
Marie  and  Levaditi: 

La  reaction  des  anticorps  syphilitiques  dans  la  paralysie  generate 
et  le  tabes,  Bull,  et  mem.  de  la  Soc.  med.  des  Hop.,  Dec.  21, 1906. 

Les  anticorps  syphilitiques  dans  le  hquide  C.  R.  des  paralytiques 
genereaux  et  des  tabetiques,  Ann.  Inst.  Pasteur,  1907,  673. 
Marie  and  Violet:  L'albumodiagnostic   dans  les  maladies  mentales, 

Congres  de  Rennes,  Aug.,  1905. 
Marie  and  Yamanouchi: 

La  reaction  de  Wassermann  dans  la  paralysie  generate,  C.  R.  de 
la  Soc.  de  Biol.,  vol.  Ixvi,  1908, 169. 

Reaction  hemolytique  comparee  du  serum  et  du  hquide  des  alienes 
paralytiques,  Soc.  med.  des  Hop.,  Feb.  20,  1908. 
Marie,  Levaditi,  and  BankowsM: 

Presence  du  treponema  pallidum  dans  trois  cerveaux  des  paraly- 
tiques generaux,  Bull,  et  Mem.  des  Hop.  de  Paris,  1913,  881. 

Presence  du  treponema  pallidum  dans  les  cerveraux  des  para- 
lytiques generaux,  C.  R.  Soc.  Biol.,  1913,  794,  lxxiv. 

Presence  constante  du  treponema  pallidum  dans  les  cerveaux  des 
paralitiques  generaux  morts  en  ictus,  Roid.,  1009. 
Marinesco:  Sur  le  diagnostic  de  la  paralysie  generate  et  du  tabes  par 

les  nouveUes  methodes,  C.  R.  de  la  Soc.  de  Biol.,  1909,  vol.  Ixvi. 
Marinesco    and    Goldstein:    Deux   cas   de   pseud o-tumeur    cerebrate; 

meningite  sereuse  et  hydrocephalic  acquise,  Nouv.  iconograph.  de 

la  Salpetriere,  1912,  vol.  xxv. 
Marinesco  and  Minea: 

Presence  du  treponema  pallidum  dans  un  cas  de  meningite  syphi- 
litique  associee  a  la  paralysie  generate  et  dans  la  paralysie  gen- 
erate, Bull.  De  l'Acad.  de  med.  Paris,  1913,  brix,  3e,  Ser.  235. 


LITERATURE  307 

Marinesco  and  Minea: 

A  propos  de  la  presence  du  treponema  pallidum  dans  le  cerveaux 

de  paralytiques  generaux,  Rev.  Neurol.,  1913,  xxi,  581. 
Relation  entre  les  treponema  pallidum  et  les  lesions  de  la  paralysie 

generate,  C.  R.  Soc.  de  Biol.,  1913,  lxxv,  231. 
Mathieu: 

Chromodiagnostic  du  liquide  C.  R.,  These  de  Paris,  1901,  No.  456. 
Contribution  a  l'etude  de  la  ponction  lombaire  dans  les  differents 

processus  meninges,  These  de  Lyon,  1904,  No.  101. 
Mauriac,  P.: 

La  seroreaction  de  Wassermann,  C.  R.  Soc.  Biol.,  1909,  666. 
Conclusions  fournies  par  300  cas  de  sero-reactions  de  Wassermann, 

C.  R.  Soc.  Biol.,  1909,  668. 
Mery:  L'examen  du  Liquide  C.  R.  et  le  diagnostic  dans  les  meningites, 

Bull,  med.,  1902,  458,  No.  39. 
Mestrezat: 

Analyses  chimique  de  liquide  C.  R.    In  Anglada,  These  de  Mont- 

pellier.    (See  Anglada,  1909.) 
Contribution  a  l'etude  chimique  du  liquide  C.  R.  Remarques  sur 

la  nature  du  principe  reducteur,  Jour,  de  phys.  et  Path,  generate, 

May,  1909,  408. 
Analuse  du  liquide  C.  R.  dans  la  meningite  cerebrospinale  a  menin- 

gocoques.      Composition    et    formule    chimique;    valeur  diag- 

nostiqueet  pronostique  de  cette  formule,  Rev.  de  med.,  1910,  189. 
Composition  chimique  du  liquide  C.  R.  normal.  Vrais  nature  de 

cette  humeure,  Bull,  de  la  Soc.  chimique,  1911,  683. 
Le  liquide  cephalo-rachidien  normal  et  pathologique;  valeur  clinique 
de  l'examen  chimique.   Syndromes  humoraux   dans  les   diverses 
affections,  Paris,  1912,  A.  Maloine. 
Mestrezat  and  Anglada:  Xanthochromic  du  liquide  C.  R.  dans  un  cas 
d'ictere   par   retention    avec   urobilin    et   hyperglycose.    Passage 
tardif  des  pigments  biliaires  dans  ce  liquide,  Compt.  rend,  de  la 
Soc.  de  Biol.,  1909,  vol.  lxvi. 
Mestrezat  and  Gaujoux: 

Analyses  du  liquide  C.  R.  dans  la  nteningite  cerebrospinale  a  men- 

ingocoques,  C.  R.  de  la  Soc.  de  Biol.,  1909,  364. 
Presence    de    nitrates  et  de  nitrites    dans  le  liquide  C.  R.  Per- 

m^abihte  meningee  aux  nitrates,  Ibid.,  1909,  424. 
Contribution  a  l'etude  du  liquide  C.  R.  dans  la  meningite  tuber- 

celeuse.   Essai  d'6tablissement   d'une   formule   chimique,   Rev. 

neurol.,  1909,  733. 
Exageration  de  la  permeability  meningee  aux  nitrates;  diagnostic 

de  la  meningite  tuberculeuse,  C.  R.  de  la  Soc.  de  Biol.,  1909,  533. 
Mestrezat  and  Roger,  H.: 

Syndrome  de  coagulation  massive,  de  xanthochromic  et  d'hemato- 

leucocytose  du  liquide  C.  R.,  Compt.  rend,  de  la  Soc.  de  Biol., 

June  7,  1909. 


308      SEROLOGY    OP    NERVOUS    AND    MENTAL   DISEASES 

Mestrezat  and  Roger,  H.:  A  propos  du  syndrome  de  coagulation  mas- 
sive et  de  xanthochromic  du  liquide  C.  R.  Eassi  de  pathogenic 

Veural  diagnostique,  Gaz.  des  Hop.,  No.  120,  p.  1495,  October  21, 

1909. 
Mignon:  La  rhinorrhee  cerebro-spinale,  Presse  Med.,  April  26,  1900. 
Milian: 

Le  liquide  C.  R.,  Steinheil,  Paris,  1904. 

Le  liquide  C.  R.  hemorragique,  Gaz.  hebdom.  de  med.  et  de  chir., 
Aug.  7,  1902, 

Le  liquide  C.  R.  des  tabetiques,  Soc.  franc,  de  dermat.  et  de  syphi- 
lographie,  April,  1903. 

La  reaction  de  Herxheimer,  Paris  Medical,  Nov.  15,  1913. 
Milian  and  Chiray:  Xanthochromie  du  liquide  C.  R.,  Bull,  de  la  Soc. 

Anat.,  June  6,  1902. 
Milliet:  De  la  valeur  diagnostique  de  la  ponction  lombaire  dans  les 

hemorragies  du  Nevraxe,  These  de  Paris,  No.  397,  1901-02. 
Moindrot:  De  la  ponction  lombaire  dans  les  tumeurs  cerebrales,  These 

de  Lyon,  No.  164,  1904. 
Moizard  and  Grenet:  La  forme  cer6bro-spinale  de  la  fievre  typhoide, 

Archives  de  medicine  des  enfants,  1903,  No.  1. 
Mollard  and  Froment:  Uree  dans  le  hquide  C.  R.  et  uremie  nerveuse, 

Jour,  de  phys.  et  de  pathol.  generate,  1909,  vol.  ii,  263. 
Mongour: 

Sur  la  teneur  du  hquide  C.  R.  en  pigments  biliaires  dans  les  icteres 
choluriques,  C.  R.  Soc.  Biol.  Seance  de  Bordeaux,  1904,  397. 

Ictere  cholemique  et  acholurique:  examen  du  hquide  C.  R.,  C.  R. 
Soc.  Biol.,  1905,  p.  518. 
Monod,  R.: 

Reactions  meningees  chez  l'enfant,  Th&se  de  Paris,  1902,  No.  77. 

Les  elements  figures  du  hquide  C.  R.  aux  cours  de  tabes  et  de  la 
paralyse  generate  progressive,  Bull.  soc.  med.  des  Hop.  de  Paris, 
Jan.,  1901.  * 

Montagnon:  Significations  de  la  reaction  albumineuse  dans  le  hquide 

C.  R.  dans  la  meningite  des  enfants,  Rev.  neur.,  1906,  1039. 
Mosny  and  Javal:  Recherches  et  dosage  des  pigments  biharies  dans  le 

hquide  C.  R.  des  icteriques,  C.  R.  Soc.  Biol.,  May  21,  1910. 
Mosny  and  Molloisel:  Saturnisme  et  lymphocytose  rachidienne,  C.  R. 

de  la  Soc.  de  Biol.,  1904,  p.  211,  vol.  lvii. 
Muttermilch:  Sur  la  nature  des  substances  qui  provoquent  la  reaction 

de  Wassermann  dans  les  serums  des  syphihtiques  et  des  lapins 

trypanosomies,  C.  R.  Soc.  Biol.,  1909,  125. 

ITALIAN  LITERATURE 

Morselh:  La  reazione  di  Wassermann  raffrontata  nel  liquido  cefalo- 
rachidiano  e  nel  sangue  dei  paralytici,  Pathologica,  1911,  3,  p.  387. 

Mya:  Sulla  quantita  del  liquido  C.  R.,  etc.,  Revista  di  patologia  nervosa 
e  mentale,  1898,  vol.  hi,  p.  385. 


LITERATURE  309 

N 
ENGLISH  LITERATURE 

Newmark:  The  Occurence  of  a  Positive  Wassermann  Reaction  in  2 
Cases  of  Non-specific  Tumor  of  the  Central  Nervous  System,  Jour. 
Amer.  Med.  Assoc,  Jan.  6,  1912. 
Nichols,  Henry  J. : 

Preliminary  Note  on  the  Action  of  Ehrlich's  Substance  (606)  on 

Spirochseta   Pertenuis   in   Animals,  Jour.  Amer.  Med.  Assoc, 

1910,  216. 
The  Present  Status  of  Salvarsan  Therapy  in  Syphilis,  Ibid.,  1912, 

603. 
Nichols  and  Fordyce:  The  Treatment  of  Syphilis  with  Ehrlich's  606, 

Ibid.,  1910,  1171. 
Nichols  and  Hough: 

Demonstration  of  Spirochseta  Pallida  in  the  Cerebrospinal  Fluid 

From  a  Patient  with  Nervous  Relapse  Following  Upon  the  Use 

of  Salvarsan,  Jour.  Amer.  Med.  Assoc,  1913,  108. 
Positive  Results  Following  the  Inoculation  of  Rabbit  with  Paretic 

Brain  Substance,  Jour.  Amer.  Med.  Assoc,  1913,  120. 
Noguchi,  H.: 

The  Relation  of  Protein,  Lipoids,  and  Salts  to  the  Wassermann 

Reaction,  Jour.  Exper.  Med.,  1909,  xi,  84. 
A  New  and  Simple  Method  for  the  Serum  Diagnosis  of  Syphilis, 

Jour.  Exper.  Med.,  1909,  xi,  392;  also  in  C.  R.  Soc  Biol.,  1909, 

456,  and  in  Munch,  med.  Woch.,  1909,  494. 
Serum  Diagnosis  of  Syphilis,  Jour.  Amer.  Med.  Assoc,  1909,  934. 
The  Butyric  Acid  Reaction  for  Syphilis  in  Man  and  Monkeys, 

Proc  Soc.  for  Exper.  Biol.  Med.,  1909,  vi,  51. 
Some  Critical  Considerations  on  the  Serum  Diagnosis  of  Syphilis, 

Ibid.,  1909,  vi,  77. 
Non-fixability  of  Complement,  Ibid.,  1909,  vii,  14. 
On  Non-specific  Complement  Fixation,  Ibid.,  vii. 
Thermostabile   Anticomplementary   Constituents   of   the   Blood, 

Jour.  Exper.  Med.,  1906,  viii,  726. 
The  Luetin  Reaction,  Jour.  Amer.  Med.  Assoc,  Oct.  5,  1912. 
Identification  of  the  Spirochseta  Pallida  in  Culture,  Ibid. 
The  Present  Status  of  the  Noguchi  System  of  Serodiagnosis  of 

Syphilis,  Interstate  Med.  Jour.,  1911,  St.  Louis,  Mo.,  Medical 

Symposium  Series,  No.  1. 
Pure  Cultivation  of  Pathogenic  Treponema  Pallidum,  Jour.  Amer. 

Med.  Assoc,  1911,  102. 
Experimental   Research  in  Syphilis  with  Especial  Reference  to 

Spirochseta  Pallida   (Treponema  Pallidum),  Jour.  Amer.  Med. 

Assoc,  1912,  1163. 
Morphological  and  Pathogenic  Variations  in  Treponema  Pallidum, 

Jour.  Exper.  Med.,  1912,  90. 


310      SEROLOGY  OF   NERVOUS   AND    MENTAL   DISEASES 

Noguchi,  H.: 

A  Cutaneous  Reaction  in  Syphilis,  Jour.  Exper.  Med.,  1911,  557. 

The  Transmission  of  Treponema  Pallidum  from  the  Brains  of 
Paretics  to  the  Rabbit,  Jour.  Amer.  Med.  Assoc,  July,  12, 
1913. 

Transmission  of  Treponema  Pallidum  from  the  Brains  of  Paretics 
to  the  Rabbit,  Jour.  Amer.  Med.  Assoc,  1913,  Ixi,  85. 
Noguchi  and  Bronfenbrenner: 

Biochemical  Studies  on  So-called  Antigen,  Jour.  Exper.  Med., 
1911,  xiii,  43. 

The  Comparative  Merits  of  Various  Complements  and  Ambo- 
ceptors in  the  Serum  Diagnosis  of  Syphilis,  Ibid.,  p.  78. 

Biochemical  Studies  on  the  Phenomena  Known  as  Complement 
Splitting,  Ibid,  1912,  xvi. 

Sublimate  and  Serum  Diagnosis  of  Syphilis,  Ibid.,  1911,  xiii. 

Barium  Sulphate  Absorption  and  Serum  Diagnosis  of  Syphilis, 
Ibid.,  1911,  xiii,  217. 
Noguchi  and  Moore: 

The  Butyric  Acid  Test  for  Syphilis  in  the  Diagnosis  of  Metasyph- 
ilitic  and  Other  Nervous  Disorders,  Jour.  Exper.  Med.,  1909,  604. 

A  Demonstration  of  the  Treponema  Pallidum  in  the  Brain  in 
Cases  of  General  Paralysis,  Jour.  Exp.  Med.,  1913,  232. 

Additional  Studies  on  the  Presence  of  Spirochseta  Pallida  in  Gen- 
eral Paralysis  and  Tabes  Dorsalis,  Jour.  Cutan.  Dis.,  1913,  xxxi, 
543. 
Nonne:  Clinical  Diagnosis  of  the  Syphilogenous  Diseases  of  the  Central 

Nervous  System,  Jour.  Amer.  Med.  Assoc,  1909,  liii,  p.  289. 
Norman  and  Rosenberger:  Purulent  Cerebrospinal  Meningitis  Pro- 
duced by  Eberth's  Bacillus  in  the  Course  of  Typhiod,  etc.,  Amer. 

Jour.  Med.  Sci.,  1908,  p.  240. 

GERMAN  LITERATURE 

Nawratzki:   Zur   Kenntnis   der  Cerebrospinalfluessigkeit,  Zeitschr.  f. 

physiol.  Chemie.,  1897,  532. 
Neisser,  A.: 

Ueber  die   Bedeutung  der  Wassermannschen  Serodiagnostik  fur 

die  Praxis,  Munch,  med.  Woch.,  1909,  p.  1076. 
Ueber  das   neue   Ehrlichsche   Mittel.,  Deut.  med.  Woch.,  1910, 

1212. 
Forschung  der  Syphilis.     Arbeit  aus  der  kais,  Gesundheitsamte, 
1911,  xxxvii. 
Neisser  and  Kuznitsky:  Bedeutung   des    Ehrlich-Hata    606  fur  die 

Syphilis  Behandlung,  Berl.  klin.  Woch.,  1910,  1485. 
Neisser  and   Siebert:  Die   Bedeutung  und  Wertung  der  serodiagnos- 
tischen  Luesreaktion  in  der  Praxis,  Jahreskurse  f.  Aerztlige  Fort- 
bildung,  April,  1910. 


LITERATURE  311 

Neisser,  Bruck,  and  Schucht:  Diagnostische  Gewebs  und  Blutunter- 

suchungen  bei  Syphilis,  Deut.  med.  Woch.,  1906,  1937. 
Neiie:    Ueber  die  "Auswertungsmethode"  des  Liquor  cerebrospinal 

vermittels  der  W.  R.,  Munch,  med.  Woch.,  1912,  121. 
Nieden :  Ueber  Lumbalpunktion,  insbesondere  die  Bef unde  bei  Kachexie, 

Inaug.  Dissert.,  Bonn,  1911. 
Niedner  and  Mamelock: 

Ueber  die  Cytodiagnose,  Wien.  med.  Blaetter,  1905,  327. 
Die  Frage  der  Cytodiagnose,  Zeitschr.  f.  klin.  Med.,  54,  p.  132. 
Nissl:  Die  Bedeutung  der  Lumbalpunktion  fuer  die  Psychiatrie,  Cen- 

tralbl.  f.  Nervenheilk.  u.  Psych.,  1904,  225. 
Nobl: 

Diagnostische  Bedeutung  der  Cerebrospinalfluessigkeit  bei  Syph- 
ilis und  den  Parasyphilitischen  Affektionen,  Berl.  klin.  Woch., 
1904,  37. 
Cuti-Reaktion  mit  waesserigen  und  alkoholischen  Extrakten,  Arch, 
f.  Dermatol.,  1910,  xcix,  434. 
Nobl  and  Arzt:  Zur  Serodiagnostik  der  Syphilis   (Porges-Meier  und 

Klausnersche  Reaktion),  Wien.  klin.  Woch.,  1908,  p.  287. 
Noble  and  Fluss:  Zur  Intrakutanreaktion  bei  Syphilis,   Ibid.,   1912, 

475. 
Noguchi,  H.: 

Ueber  gewisse  chemische  komplementsubstanzen,  Biochem.  Zeit- 
schr., 1907,  vii,  327. 
Ueber  chemische  Inaktivierung  und  Regeneration  der  Komple- 

mente,  Biochem.  Zeitschr.,  1907,  vi,  172. 
Die  W.  R.  und  der  praktische  Arzt.,  Miinch.  med.  Woch.,  1910, 

1399. 
Weitere  Erfahrungen  mit  vereinfachter  Methode  der  Serumdiag- 
nose  der  Syphilis,  Zeitschr.  f.  Immunitaetsforsch,  1910,  vii,  353. 
Die  quantitative  Seite  der  W.  R.  mit  Bemerkungen  ueber  den 
Globulin     und     natuerlichen     antihammel     Amboceptorgehalt 
syphilitischer    Sera,    sowie    ueber    die    angebliche    Gefahr   von 
Auftreten  des  Neisser-Sachs'schen  Phaenomens  beim  Verwenden 
des  antimenschlichen  Amboceptors,  Ibid.,  1911,  x. 
Ueber  die  Gewinnung  der  Reinkulturen  von  pathogener  Spiro- 
chaeta  pallida  und  von  Spir.  pertenuis,  Miinch.  med.  Woch., 
1911,  1550. 
Hautallergie  bei   Syphilis,   ihre   diagnostische  und  prognostische 

Bedeutung,  Miinch.  med.  Woch.,  1911,  2372. 
Studien  ueber  den  Nachweis  der  Spirochaeta  pallida  im  Central- 
nervensystem  bei  progressiven  Paralyse  und  bei  Tabes  dorsalis, 
Miinch.  med.  Woch.,  1913,  lv,  737. 
Nonne : 

Die  Diagnose  der  Syphilis  bei  Erkrankungen  des  Zentralnerven- 

systems,  Centralbl.  f.  Nervenheilk.  u.  Psych.,  1908,  p.  974. 
Syphilis  und  Nervensystem,  Berlin,  1909,  2d  ed.,  p.  631. 


312      SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

Nonne : 

Die  Diagnose  der  Syphilis  bei  Erkrankungen  des  zentralen  Ner- 
vensystems  mit  besonderer  Beruecksichtigung:  (a)  der  cytolo- 
gischen  nnd  chemischen  Ergebnisse  der  diagnostischen  Lumbal- 
punktion;  (6)  der  serodiagnostischen  Untersuchungen  am  Blute 
und  an  der  Lumbalfiuessigkeit,  speziell  bei  der  Tabes  und  Para- 
lyse, Deut.  Zeitschr.  f.  Nervenh.,  1908,  p.  36. 

Weitere  Erfahrungen  (Bestaetigungen  und  Modifikationen)  ueber 
die  Bedeutung  der  "Vier  Reaktionen"  (Pleocytose,  Phase  I, 
der  W.  P.,  im  Blut-serum  und  im  Liquor  spinalis)  fuer  die  Diag- 
nose der  syphilogenen  Hirn  und  Rueckenmarks  Krankheiten, 
Deut.  Zeitschr.  f.  Nervenheilk.,  1910,  38. 

Ueber  das  Vorkommen  von  starker  "Phase  I  Reaktion"  bei  fehlen- 
der  Lymphocytose  bei  6  Faellen  von  Rueckenmarkstumor, 
Ibid.,  1910,  p.  161. 

Der  heutige  Standpunkt  der  Lehre  von  der  Bedeutung  der  "Vier 
Reaktionen"  fuer  die  Diagnose  und  differentialdiagnose  organ- 
ischer  Nervenkrankheiten,  Ibid.,  1911,  p.  201. 

Ueber  Wert  und  Bedeutung  der  modernen  Syphilistherapie  fuer 
die  Behandlung  von  Erkrankungen  des  Nervensystems,  Ibid., 
1912,  vol.  xliii. 

Klinische  und  anatomische  Untersuchung  eines  Falles  von  isolierter 
Pupillenstarre  ohne  Syphihs  bei  Alkoholismus  Chronicus  gravis, 
Neurol.  Centralblatt,  1912,  No.  1. 
Nonne  and  Apelt: 

Ueber  fraktionierte  Eiweissausfaellung  in  der  Spinalfluessigkeit 
von  Gesunden,  Luetikern,  funktionell  und  organisch-Nerven- 
kranken  und  ihre  Verwertung  zur  Differentialdiagnose  der 
Dermentia  paralytica,  Tabes  dorsalis,  tertiaeren,  und  abge- 
laufenen  Syphihs,  Arch.  f.  Psych,  u.  Nervenh.,  1907,  vol.  xliii. 

Ueber  Lymphocytose  und  Globulinuntersuchung  der  Spinalflues- 
sigkeit bei  organische  Nervenkrankheiten,   Neurol.  Centralbl., 
1908,  181. 
Nonne  and  Hauptmann:  Liquor  cerebrospinalis  und  W.  R.,  Neurol. 

Centralbl.,  1912,  No.  2. 
Nonne  and  Holzmann: 

Weitere  Erfahrungen  ueber  den  Wert  der  neueren  cytologischen, 
chemischen  und  biologischen  Untersuchungsmethoden  fuer  die 
Differentialdiagnose  der  syphilogenen  Erkrankungen  des  Zen- 
tralnervensystems,  gesammelt  an  295  neuen  Faellen  von  organ- 
ischen  Erkrankungen  des  Hirns  und  des  Rueckenmarks,  Deut. 
Zeitschr.  f.  Nervenheilk.,  1909,  p.  195,  vol.  xxxvii. 

Ueber  W.  R.  im  Liquor  spinahs  bei  Tabes  d.  sowie  ueber  quanti- 
tative Auswertung  von  Staerkegraden  der  W.  R.  bei  syphilogenen 
Erkrankungen  des  Zentralnervensystems,  Monatschr.  f.  Psych, 
und  Neurologie,  1910,  p.  128. 


LITERATURE  313 

FRENCH  LITERATURE 

Nageotte:  Limite  de  la  lymphocytose  physiologique,  C.  R.  Soc.  Biol., 

Dec.  14,  1907. 
Nageotte  and  Levi-Valensi :  Numeration  directe  des  elements  cellu- 

laires  du  liquide  C.  R. :  limites  physiologiques  de  la  lymphocytose, 

Comptes  rend,  de  la.  Soc.  de  Biol.,  1907,  603. 
Nageotte,  Madam:  Numeration  directe  des  elements  figures  du  liquide 

C.  R.,  Soc.  Pediatr.,  April  25,  1911. 
Nanu-Musell  and  Vasiliu:  La  reaction  de  Wassermann  dans  la  malaria, 

Sem.  med.,  1910,  No.  6. 
Netter:  Formes  meningitiques  de  la  fievre  typhoide;  leur  frequence  et 

leur  importence  pronostique.  Utilite  de  la  recherche  du  signe  de 

Kernig.  Characteres  du  liquide  retire  par  la  ponction,  Soc.  med. 

des  Hop.,  April  15,  1904. 
Netter  and  Clerc:  Hemorragie  des  meninges  medullaires,  reinseigne- 

ments  fournis  par  la  ponction  lombaire,  Ibid.,  July  25,  1900. 
Netter  and  Debre:  Liquide  C.  R.  au  cours  des  meningites  cerebro- 

spinales  (premiere  note)  Liquide  clairs  pendant  23  premieres  heures 

de  la  maladie,  C.  R.  Soc.  Biol.,  1909,  866. 
Netter  and  Gendron: 

Liquide  Cephalo-rachidiens  limpides  au  cours  de  meningites 
c6rebro-spinales  (Deuxieme  note)  Liquide  clairs  a  une  periode 
avancee  de  la  maladie,  Ibid.,  1909,  p.  1009. 

Troisieme  note.  Liquide  normaux  depourvus  des  microbes  dans 
les  formes  attenues  et  abortives.  Pouvoir  agglutinant  du  sang 
vis  a  vis  du  meningocoque,  Ibid.,  1909,  1252. 

Modifications  consecutives  a  l'introduction  du  serum  humain  dans 
le  canal  rachidien,  Ibid.,  1910,  550. 
Nicholas,   Favre,   and  Gautier:    Intra-dermo-reaction  et   cuti-reaction 

avec  la  syphiline  chez  les  syphilitiques,  C.  R.  Soc.  Biol.,  1910,  257. 
Nicloux:  Permeabilite  a  l'alcool,  C.  R.  Soc.  Biol.,  1900,  p.  621. 
Noguchi : 

Decouverte  du  treponeme  pale  dans  les  cerveaux  de  paralytiques 
generaux,  C.  R.  Soc.  Biol.,  1913,  lxxiv,  349. 

Serodiagnostic  de  la  syphilis,  Traite"  sur  le  sang  humain,  Gilbert 
and  Weinberg,  Paris,  1912. 
Norman:  Meningite  uremique,  Loire  Medicale,  1911. 

ITALIAN  LITERATURE 

Nizzi:  La  reazione  de  Wassermann  in  rapporto  a  lesioni  sperimentali 
della  sostanza  nervosa  centrale,  Rivista  sperim.  de  freniatria,  1910, 
36. 


314      SEROLOGY  OF   NERVOUS  AND   MENTAL   DISEASES 


GERMAN  LITERATURE 

Ohm:  Einiges  ueber  die  diangostische  Bedeutung  des  Blutgehaltes  und 

der  Lymphocytose  im  Liquor  Cerebrospinalis.  (Zugleich  ein  Bei- 

trag  zur  Kasuistik  der  basalen  Hirnaneurysmen),  Deutsche  med. 

Woch.,  1906,  p.  1694. 
Opitz:  Ueber  die  Bedeutung  der  W.  R.  fuer  die  Geburtshilfe,  Med. 

Klin.,  1908,  p.  1137. 
Oppenheim:  Ueber  Lecithinwirkung  bei  Syphilis,  Wien.  klin.  Woch., 

1908,  679. 
Orgelmeister:  Zum  diagnostischen  Wert  der  Lumbalpunktion,  Deutsch. 

Arch.  f.  klin.  Med.,  1903,  p.  142. 
Orth:  Ueber  die  Exsudatzellen  im  allgemeinen  und  die  Exsudatzellen 

bei  verschiedenen  Formen  der  Meningitis  im  besonderen,  Reference 

in  Munch,  med.  Woch.,  1906,  No.  3. 
Ossipow:  Ueber  die  pathologische  Veraenderungen  welche  in  dem  Zen- 

tralnervensystem  von  Thieren  durch  die  Lumbalpunktion  hervor- 

gerufen  werden,  Deut.  Zeitschr.  f.  Nervenheilk.,  1902,  vol.  xix. 

FRENCH  LITERATURE 

Obregia:  La  ponction  cervicale,  Compt.  r.  Soc.  Biol.,  1908,  vol.  lxiv. 
Obregia  and  Bruckner: 

Le  liquide  C.  R.  dans  la  paralyse  generale  stationaire  soumise  a 

la  reaction  de  Wassermann,  C.  R.  Soc.  Biol.,  1909,  lxvi. 
Resistance  a  la  putrefaction  de  l'anticorps  syphilitique,  C.  R.  Soc. 
Biol.,  1909,  lxvi,  p.  482. 
Olmer  and  Tian: 

Presence  de  Thalium  dans  le  liquide  C.  R.  apres  l'intoxication  par 

l'acetate  de  ThaUum,  C.  R.  Soc.  Biol.,  Dec.  15,  1908. 
Permeabilite  de  meninges  normales  au  salicylate  de  hthium,  C.  R. 
Soc.  Biol.,  May  18,  1909. 

ITALIAN  LITERATURE 

Orefici:  Sul  passaggio  del  bromo  et  del  iodo  nel  liquido  C.  R.  dei  Bam- 
bini, Vlth  Congres  de  Pediatrie  Italian,  Oct.,  1907. 

Ormea:  Sulle  modificazioni  della  pressione  sub-archnoidiana  e  del 
caratteri  del  liquido  cerebro-spinale  nell'epilessia  sperimentale, 
Revista  sperimentale  di  Freniatria,  1902,  vol.  xxviii,  p.  40. 

P 

ENGLISH  LITERATURE 

Parkinson:  Note  on  the  Cerebrospinal  Fluid  in  General  Paralysis  of  the 
Insane,  Archives  of  Neurology,  1909. 


LITERATURE  315 

Peabody,  W.  F.,  George  Draper,  and  Dochez,  A.  R. :  A  Clinical  Study  of 

Acute  Poliomyelitis,  Monograph  of  the  Rockefeller  Inst,  for  Med. 

Research,  New  York,  1912. 
Pedersen,  V.  C:  Serodiagnosis  of  Syphilis,  N.  Y.  Med.  Jour.,  1910, 

pp.  947,  1012,  1063,  1113. 
Pomroy:  The  Diagnostic  Value  of  Lumbar  Puncture  in  Psychiatry, 

Jour,  of  Nerv.  and  Ment.  Dis.,  1907,  p.  225. 

GERMAN  LITERATURE 
Pandy:  Ueber  eine  neue  Eiweissprobe  fuer  die  Cerebrospinalfluessig- 

keit,  Neurol.  Centralbl.,  1910,  p.  915. 
Panzer: 

Zur  Kenntniss  der  Cerebrospinalfluessigkeit,  Wien.  klin.  Woch., 

1899,  805. 

Ueber  die  Polynukleose  im  Liquor  cerebrospinalis,  insbesondere 
bei  der  progressiven  Paralyse,  Zeitschr.  f.  die  gesamte  Neurol. 
Psych.,  1911,  vol.  iv. 
Pappenheim,  M: 

Ueber  paroxysmale  Fieberzustaende  bei  prog.  Paralyse  mit  Ver- 
mehrung  der  polynukleaeren  Leukocyten  im  Blute  und  in  der 
Cerebrospinalfluessigkeit,  nebst  Bemerkungen  ueber  Blut  und 
Liquor  bei  Exacerbationen  des  paralytischen  Prozesses,  Monat- 
schr.  f .  Psych,  u.  Neurol.,  1907,  vol.  xxxi,  Heft  6. 

Beitrage  zum  Zellstudium  der  Cerebrospinalfluessigkeit,  Zeitschr. 
f.  Nervenheilk.,  1907,  p.  315. 

Faerbung  der  Ze  len  des  Liquor  cer.  spin,  mit  und  ohne  Zusatz 
von  Eiweiss,  Wien.  klin.  Woch.,  1907,  vol.  xx. 

Zum  Wesen  der  Komplementbindungsreaktion  der  Cerebrospi- 
nalfluessigkeit, Deutsche  Zeitschr.  f .  Nervenheilk.,  Sept.  30, 1908. 

Ueber  die  Polynukleose  im  Liquor  Cerebrospinalis,  insbesondere 
bei  der  progressiven  Paralyse,  Zeitschr.  f .  die  gesamte  Neurol,  u. 
Psych.,  1911,  267. 
Peritz,  G.: 

Ueber  das  Verhaeltniss  von  Lues,  Tabes,  und  Paralyse  zum  Le- 
cithin, Zeitschr.  f.  Exper.  Path.  u.  Ther.,  1908,  9,  607. 

Lues,  Tabes,  und  Paralyse  in  ihren  therapeutischen  Beziehungen 
zum  Lecithin,  Berl.  klin.  Woch.,  1908,  vol.  xlv,  p.  607. 
Pfaundler: 

Physiologisches,  Bakteriologisches,  und  Klinisches  ueber  die  Lum- 
balpunktion,  Beitrage  zur  klin.  Med.,  1899,  20. 

Lumbalpunktion  bei  Kindern,  Jahresbl.  f.  Kinderheilkunde,  1899, 
p.  264. 
Pick,  E.  P.:  Darstellung  der  Antigene  mit  chemischen  und  physikal- 

ischen  Methoden,  Handbuch  der  Immunitaetsfor.,  1908,  p.  568, 

vol.  i. 
Pick   and   Proskauer:   Die   Komplementbindung   als   Hilfsmittel   der 

anatomischen  Syphilisdiagnose,  Med.  Klin.,  1908,  p.  539. 


316      SEROLOGY    OF    NERVOUS   AND    MENTAL    DISEASES 

Pick,  W.:  Bericht  ueber  die  bisherigen  Resultate  der  Behandlung  der 

Syphilis   mit    dem    Praeparate   von    Ehrlich-Hata    (120    Faelle), 

Wien.  klin.  Woch.,  1910,  No.  33. 
Pieper:  Die  Essigsauere  Probe  zur  Unterscheidung  der  Exsudate  und 

Transudate,  Munch,  med.  Woch.,  Jan.  4,  1910. 
Pighini : 

Ueber  den  Cholesteringehalt  der  Lumbalfluessigkeit  einiger 
Geisteskrankheiten,  Zeitschr.  f.  phys.  Chemie,  1909,  p.  518. 

Cholesterine  und  die  W.  R.,  Centralbl.  f.  Nervenheilk.  und 
Psych.,  1909,  775. 

Chemische  und  biochemische  Untersuchungen  ueber  das  Nerven- 
system  unter  normalen  und  pathologischen  Bedingungen,  Drei 
Mittheilungen  in  der  Biochemischen  Zeitschr.,  1912,   129. 

Ueber   die    Indophenolexydase   im   Zentralnervensystem   in   der 
Tela  choroidea  und  in  der  Cerebrospinalfluessigkeit,  Ibid. 
Pighini  and  Barberi:  Untersuchungen  ueber  Katalase  im  Liquor  cere- 

brospinalis,  Ibid. 
Pighini  and  Nizzi:    Aufsuchung  der  Esterase  und  Lecithase  in  der 

normalen  und  pathologischen  Cerebrospinalfluessigkeit,  Ibid. 
Pilcz:  Zur  diagnostischen  Bedeutung  der  Lumbalpunktion,  Wien.  klin. 

Rundschau,  1907,  425. 
Plaut,  F.: 

Die  Wassermannsche  Serodiagnostik  der  Syphihs  in  ihrer  Anwen- 
dung  auf  die  Psychiatire,  1909,  Fischer,  Jena. 

Ueber  dass  Vorhandensein  luetischer  Antistoffe  in  der  cerebro- 
spinalfluessigkeit, Neurol.  Centralbl.,  1906,  p.  1127. 

Untersuchungen  zur  Syphilisdiagnose  bei  Dementia  paralytika 
und  Lues  Cerebri,  Monatschr.  f.  Psych,  u.  Neurol.,  1907,  p.  95. 

Ueber  den  gegenwertigen  Stand  des  serologischen  Luesnachweises 
bei  den  syphilogenen  Erkrankungen  des  Centralnervensystems, 
Munch,  med.  Woch.,  1907,  p.  1468. 

Die  Lues  Paralyse  Frage.  Jahresversam.  des  Deutsch,  Vereins 
f.  Psych.,  Koeln  und  Bonn,  April  23  and  24,  1909;  Allgemeine 
Zeitschrift  f.  Psych.,  1909,  66. 

Die  W.  R.  und  der  praktische  Arzt,  Miinch.  med.  Woch.,  1910,  No. 
10. 

Die  Bedeutung  der  W.  R.  fuer  die  Psychiatrie,  Zeitschr.  f.  die 
gesamte  Neurol,  u.  Psych.,  1911,  p.  39. 

Die  W.  R.  in  der  Psychiatrie  und  Neurologie,  Ueberblick  ueber 
die  Arbeiten  des  Jahres  1909;  Ibid.,  1910,  Ref.  1. 

Ueber  das  Vorhandensein  luetischer  Antistoffe  in  der  Cerebro- 
spinalfluessigkeit von  Paralytikern,  Berl.  klin.  Woch.,  1907, 
144. 

Serodiagnostik  der  Syphilis,  Centralbl.  f .  Nervenheilk.  und  Psychi- 
atrie, 1908,  xxxi,  p.  289. 

Die  Wassermannsche  Serodiagnostik  bei  erworbener  und  here- 
ditaerer  Syphihs  des  Zentralnervensystems,  Ibid.,  1908,  975. 


LITERATURE  317 

Plaut  and  Goering:  Untersuchungen  an  Kindern  und  Ehegatten  von 

Paralytikern,  Munch,  med.  Woch.,  1911,  No.  xxxvii. 
Plaut  and  Heuck:  Zur  Fornetschen  Praecipitaetreaktion  bei  Lues  und 

Paralyse,  Berl.  klin.  Woch.,  1908,  p.  1141. 
Plaut,  Rehm,  O.,  and  Schottmueller :  Leitfaden  zur  Untersuchung  der 

Cerebrospinalfluessigkeit,  1913,  Fischer,  Jena. 
Poetzl,  Eppinger,  and  Hess :  Ueber  Funktionspruef ungen  des  vegetativen 

Nervensystems  bei  einigen  Gruppen  von  Psychosen,  Wien.  klin. 

Woch.,  1910,  1831. 
Popper  and  Zak:  Ueber  die  klinische  Bedeutung  des  Essigsauerenach- 

weis  in  seroesen  Fluessigkeiten,  Wien.  klin.  Woch.,  1910,  No.  21. 
Porges,  Otto: 

Technik  und  Methodik  der  Serodiagnostik  der  Lues  mit  Hilfe  der 
Ausflockungsmethode,  Kraus  and  Levaditi,  Handbuch  der 
Immunitaetsforsch,  1909,  1182. 

Die  Beziehungen  der  Lipoide  zur  Immunitaetslehre,  Ibid.,  1909, 
pp.  1162,  1181. 
Porges  and  Meier:  Rolle  der  Lipoide  bei  der  Wassermannschen  Syphilis- 

reaktion,  Berl.  klin.  Woch.,  1908,  p.  731. 

FRENCH  LITERATURE 

Parisot : 

La  pression  du  liquide  C.  R.  chez  l'homme  a  l'etat  normal  et  patho- 
logique,  XIX  Congres  des  medicins  ahenistes  et  neurologistes 
de  France  et  des  pays  de  langue  francaise,  Nantes,  April  2,  1909. 

Le  role  de  modifications  de  pression  du  liquide  C.  R.  dans  la  symp- 
tomatologie  de  diverses  affections,  Revue  med.  de  l'Est,  Feb. 
15,  1910,  p.  97. 
Pauly:  Meningite  tuberculeuse  sans  reaction  leucocytaire  du  liquide 

C.  R.,  Lyon  med.,  1906. 
Pavy:  Les  hemorragies  meningees  a  forme  memngitique,   These  de 

MontpeUier,  No.  51,  1905. 
Percheron:  Le  diagnostic  de  la  meningite  tuberculeuse  chez  l'enfant. 

Valeur  de  la  ponction  lombaire,  These  de  Paris,  1903,  No.  442. 
Petit,  A.,  and  Girard,  J.:  Sur  la  fonction  secretaire  des  plexus  choroides, 

Archives  d'anatomie  microscopique,  Sept.,  1902,  p.  224. 
Pitres:  Lymphocytose  du  liquide  C.  R.  dans  trois  cas  de  nevralgie 

trijumeau,  C.  R.  Soc.  Biol.,  1904,  p.  270. 
Pust:  Contribution  a  l'etude  de  la  valeur  de  la  ponction  lombaire  et 

du  signe  de  Kernig  dans  le  diagnostic  des  meninges  tuberculeuses 

de  l'enfance,  These  de  Toulouse,  1907,  No.  67. 

ITALIAN  LITERATURE 

Paegna:  L'examen  cytologique  du  liquide  C.   R.  dans  les  maladies 
mentales,  Annali  di  Neurologia,  xxiv,  1906. 


318      SEROLOGY   OF    NERVOUS   AND    MENTAL   DISEASES 

Pende,  N.:  Meningite  syphilitique,  Accademia  italiana  di  Roma,  1906. 

Pighini :  La  colesterina  nel  liquido  cef alo-rachidiano  dei  paralitici,  e  sua 

partecipiazione  alia  reazione  di  Wassermann,  Rif .  medica,  xxv,  1909. 


GERMAN  LITERATURE 
Quincke: 

Ueber  Lumbalpunktion,  Berl.  klin.  Woch.,  1895,  No.  41. 

Zur  Physiologie  der  cerebrospinalfluessigkeit,  Arch.  f.  Anat.  u. 
Physiol.,  1878,  153. 

Die  Lumbalpunktion  des  Hydrocephalus,  Berl.  klin.  Woch.,  1891, 
No.  38. 

Ueber   Meningitis   serosa   und   verwandte   Zustaende,    Deutsche 
Zeitschrift  f.  Nervenheilk.,  1896. 

Zur  Pathologie  der  Meningen,  Ibid.,  1910,  No.  40. 

Diagnostische   und   therapeutische  Bedeutung  der  Lumbalpunk- 
tion, Deut.  med.  Woch.,  1905. 


R 
ENGLISH  LITERATURE 

Rae:  The  Diagnostic  Value  of  Rachicentesis,  Brit.  Med.  Jour.,  June  17, 

1911. 
Robertson  and  Brown:  The  Bacteriology  of  the  Cerebrospinal  Fluid 

in  General  Paralysis  of  the  Insane,  Jour,  of  Mental  Sci.,  1909,  56. 
Robinson,  D.  M.,  and  Orleman: 

The  Noguchi  Method  of  Serum  Diagnosis  of  Syphilis,  its  Practical 
Value,  Med.  Rec,  July  23,  1910. 

Diagnostic  Value  of  the  Noguchi  Luetin  Reaction  in  Dermatology, 
Jour,  of  Cutan.  Dis.,  July,  1912. 
Rosanoff  and  Wiseman:  Syphilis  and  Insanity,  Amer.  Jour,  of  Insan., 

1910,  419. 
Rosenheim: 

New  Tests  for  Cholin  in  Physiological  Fluids,  Jour,  of  Physiol., 
1905,  p.  220. 

Cholin  in  the  Cerebrospinal  Fluid,  Jour,  of  Physiol.,  1906-7,  405. 
Ross:  The  Application  of  Certain  New  Chemical  Tests  to  the  Diagnosis 

of  General  Paralysis  and  Tabes,  Brit.  Med.  Jour.,  May  8,  1909. 
Ross  and  Jones:  On  the  Use  of  Certain  New  Chemical  Tests  in  the 

Diagnosis  of  General  Paralysis  and  Tabes,  Brit.  Med.  Jour.,  1909, 

1111. 
Rous,  P.  F.:  Clinical  Studies  of  the  Cerebrospinal  Fluid  with  Especial 

Reference  to  Pressure,  and  the  Number  and  Character  of  the  Cells, 

Amer.  Jour.  Med.  Sci.,  April,  1907,  567. 


LITERATURE  319 

GERMAN  LITERATURE 

Ranke:  Die  Lumbalpunktion  bei  der  tuberkuloesen  Gehirnhautent- 

zuendung  des  Kindesalters,  Munch,  med.  Woch.,  1897,  38. 
Ranzi:  Ueber  Komplementablenkung  durch  Serum  und  Organe,  Wien. 

klin.  Woch.,  1906,  1552. 
Raven: 

Die  Bedeutung  der  isolierten  Eiweisvermehrung  und  der  Xantho- 
chromie  im  Liquor  cerebrospinahs  fuer  die  Diagnose  von  Kom- 
pression  des  Rueckenmarks.   Erfahrungen  an  15  durch  Operation 
oder  Sektion  diagnostisch  sichergestellten  Faellen,  Deut.  Zeit- 
schr.  f .  Nervenheilk.,  1912,  380. 
Die  Bedeutung  der  isolierten  Eiweisvermehrung  und  der  Xantho- 
chromic im  Liquor  Cerebrospinahs,  Ibid.,  Band  44,  Seite  380. 
Redhch,  Poetzl,  and  Hess:  Untersuchungen  ueber  das  Verhalten  des 
Liquor  cerebrospinahs  bei  Epilepsie,  Zeitschr.  f.  d.  ges.  Neur.  u. 
Psych.,  1910,  715,  492. 
Rehm: 

Die     Zerebrospinalfluessigkeit.     Physikahsche,     chemische,     und 

cytologische    Eigenschaften    und    ihre   khnische    Verwertung, 

Histologische   und   Histopathologische  Arbeiten,  v.  Nissl   und 

Alzheimer,  vol.  iii,  p.  2,  1909  (Literature). 

Weitere  Erfahrungen  in  dem  Gebiete  der  Lumbalpunktion,  Cen- 

tralbl.  f.  Neurol,  u.  Psych.,  1905,  No.  119. 
Ueber  den  Wert  cytologischer  Untersuchung  der  Cerebrospinal- 
fluessigkeit   fuer    die    Differentialdiagnose,    Ref.    Centralbl.   f. 
Nervenheilk.  u.  Psych.,  1907. 
Ergebnisse   der   cytologischen    Untersuchung   der   Cerebrospinal- 
fluessigkeit  und  deren  Aussichten,  Munch,  med.  Woch.,  1908, 
31. 
Cytologic  der  Cerebrospinalfluessigkeit  und  deren  diagnostische 
Verwertbarkeit,  Ref.  Zeitschr.  f.  d.  Ges.  Neurol,  u.  Psych.,  1912, 
p.  481. 
Reicher:  Ueber  W.  R.  und  Narkose,  Deut.  med.  Woch.,  1910,  617. 
Reichmann : 

Zur    Technik    der    Lumbalpunktion  und  der   Untersuchung  des 

Liquor  cerebrospinahs,  Miinch.  med.  Woch.,  1912,  468. 
Zur  Physiologie  und  Pathologie  des  Liquor  cerebrospinahs,  Deut. 
Zeitschr.  f.  Nervenheilk.,  1911,  No.  42. 
Reinhardt: 

Ueber  positive  W.  R.  bei  Lepra,  Framoesie  und  Scharlach,  Miinch. 

med.  Woch.,  1909,  2197. 
Erfahrungen  mit  der  W.  R.,  Miinch.  med.  Woch.,  1909,  2092. 
Richter:  Beitrage  zur  diagnostischen  Verwertung  der  Cerebrospinal- 
fluessigkeit in  der  Psychiatrie,  Zeitschr.  f.  d.  ges.  Neur.  u.  Psych., 
1910,  318. 
Rieken:  Ueber  Lumbalpunktion,  Deut.  f.  klin.  Med.,  1895,  Bd.  56. 


320      SEROLOGY   OF   NERVOUS   AND    MENTAL   DISEASES 

Rindfleisch:  Ueber  diffuse  Sarkomatose  der  Meningen  mit  charakter- 

istischer  Veraenderung  des  Liquor  cerebrospinalis,  Deut.  Zeitschr. 

f.  Nervenheilk.,  1904,  p.  144. 
Roemheld:  Zur  Klinik  postdiphtherischer  Laehmungen  und  Liquor- 

befund  bei  postdiphtherischer  Pseudotabes,  Ref.  Neur.  Zentralbl., 

1908,  1007. 
Roily:  Die  Wassermannsche  Seroreaktion  bei  Lues  und  anderen  Infek- 

tions  krankheiten,  Munch,  med.  Woch.,  1909,  62. 
Rosenfeld:  Ueber  das  Cholin,  Neurol.  Centralbl.,  1904,  632. 
Rossi,  O.:  Beitrage  zur  Kenntniss  der  in  der  Cerebrospinalfluessigkeit 

enthaltenen  reduzierenden  Substance,  Zeitschr.  f.  phys.  Chemie, 

July,  1903,  p.  183. 
Rotstadt:   Ueber   die   Cerebrospinalfluessigkeit   unter   normalen   und 

pathologischen  Verhaeltnissen,  Ref.  Zeitschr.  f.  d.  ges.  Neur.  u. 

Psych.,  1912,  483. 

FRENCH  LITERATURE 

Rabinivitch  and  Levaditi:  Role  de  la  syphilis  dans  l'etiologie  de  la 

demence  precoce,  C.  R.  Soc.  Biol.,  1909,  889. 
Ramond,  L.:  Pleuro-tuberculose  primitive  et  meningite  tuber culeuse. 
Etude  comparee  du  liquide  pleurale  et  C.  R.,  These  de  Paris,  Jan., 
1907,  No.  132. 
Ravaut : 

Le  liquide  C.  R.  de  syphilitiques  en  period  secondaire,  Ann.  de 

dermat.  et  de  Syph.,  1903,  537. 
Etudes  cytologiques  de  liquide  C.  R.  chez  les  syphihtiques,  Ibid., 

1903,  p.  1 ;  Lyon  medicale,  1903. 
Le  liquide  C.  R.  au  course  de  la  syphilis  acquise  et  hereditaire, 

Rev.  mens,  de  med.  int.  et  de  therap.,  1909,  273. 
Les  indications  cliniques  et  therapeutiques  fournies  par  la  ponction 
lombaire  au  course  de  la  syphilis  acquise  et  hereditaire,  Mond. 
med.,  Oct.  5,  1911,  No.  428. 
Ravaut  and  Darre: 

Contribution  a  Petude  des  Herpes  geniteaux.    Etudes  du  liquide 

C.  R.,  Gaz.  des  Hop.,  Oct.  15,  1903,  No.  119. 
Etudes  des  reactions  meningees  dans  un  cas  de  syphilis  heredi- 
taire, Ibid.,  1907   207. 
Ravaut,  Gastinel,  and  Velter:  La  rachicentese,  Monograph,  Critzman, 

May  31,  1910,  Masson,  Paris. 
Raviart,  Breton,  and  Petit :  Recherches  sur  la  reaction  de  Wassermann 

chez  400  alienes,  C.  R.  Soc.  Biol.,  Feb.  29,  1908. 
Raymond  and  Sicard:  Liquide  C.  R.  au  course  de  l'hydrargyrisme 
chronique,  Presence  de  Hg.  Revue  neurologique,  1902,  T.  10, 
p.  467. 
Renard,  Rene,  Joltrain,  E. :  Resultats  compares  de  la  methode  de  Was- 
sermann et  d'une  methode  de  simplification  pratique  pour  le  diag- 
nostic de  la  syphilis,  C.  R.  Soc.  Biol.,  1910,  241. 


LITERATURE  321 

Renon  and  Monier,  Villard:  Paralysie  ascendente  de  Landry;  Guerison. 

Modifications  chimiques  du  liquide  C.  R.,  Soc.  med.  des  Hop., 

July,  1899,  No.  24. 
Renon  and  Tixier: 

Examen  cytologique  dans  un  cas  de  meningite  tuberculeuse,  pres- 
ence d'une  notable  quantite  d'albumine  dans  le  liquide  C.  R., 
Soc.  med.  des  Hop.,  June  8,  1906,  p.  579. 

Sur  les  albumines  du  liquide  C.  R.  pathologique,  C.  R.  Soc.  Biol., 
1906,  639. 
Riedel:  Contribution  a  l'etude  du  liquide  C.  R.  et  sang  dans  l'epilepsie, 

Archivos  brasilieros  di  Psychiatria,   Neurologia,   Medicina  legal, 

1908,  pp.  235-287. 
Robert:  La  ponction  lombaire.  Deux  ans  de  pratique  dans  un  service 

de  maladies  mentales,  These  de  Bordeaux,  No.  101,  1905. 
Robinson,  D.  M.,  and  Orleman:  La  methode  de  Noguchi  dans  le  sero- 

diagnostic  de  la  syphilis,  avec  quelques  considerations  pratiques 

et  serologiques,  Ann.  de  maladies  vener.,  1910,  881. 
Rocaz:    Du   diagnostic  de   la   meningite   tuberculeuse   chez    1' enfant: 

Meningites  et  pseudo-meningites  de  l'enfance:  Valeur  diagnostique 

de  la  ponction  lombaire,  Gaz.  hebd.  des  sciences  med.  de  Bordeaux, 

Jan.,  1902,  No.  2,  p.  3. 
Rombach  and  De  Josselin  de  Jong:   Meningitis   gonorrhoica,   Ned. 

Tijdschr.  v.  Geneesk.,  1907,  1262. 
Roubinovitch  and  Paillard: 

Le  liquide  C.  R.  dans  diverses  maladies  mentales,  C.  R.  Soc.  Biol., 
1910,  p.  582. 

Le  liquide  C.  R.  dans  les  maladies  mentales,  Revue  gener.  en  Gaz. 
des  Hop.,  Feb.  11  and  18,  1911,  Nos.  17  and  20. 


ENGLISH  LITERATURE 

Sabrazes,  J.,  Eckstein,  and  Kenneth:  Note  on  a  Simple  Method  of  Fix- 
ation of  the  Complement  in  Syphilis,  Lancet,  1910,  232. 

Sawyer:  The  Value  of  Cytodiagnosis  in  Practical  Medicine,  Lancet, 
1908,  283. 

Schaller,  W.  F.:  A  Report  of  Analysis  of  the  Cerebrospinal  Fluid  with 
Clinical  Notes  in  109  Cases  of  Disease  of  the  Nervous  System,  Not 
Including  the  Acute  Meningeal  Affections,  Jour,  of  Nerv.  and 
Ment.  Dis.,  Aug.,  1913. 

Schoelberg  and  Goodall:  On  the  Wassermann  Reaction  in  172  Cases  of 
Mental  Disorder  and  66  Control  Cases,  Syphilitic  and  Other,  with 
Historical  Survey  for  the  Years  1906-10,  inclusive;  Comments 
and  Conclusions,  Jour,  of  Ment.  Sci.,  1911,  237. 

Simon:   Complement   Fixation   in   Malignant   Diseases,    Jour.    Amer. 
Med.  Assoc,  1909,  1090. 
21 


322      SEROLOGY    OF  NERVOUS    AND    MENTAL  DISEASES 

Simon  and  Thomas:  Complement  Fixation  in  Malignant  Diseases, 

Jour.  Amer.  Med.  Assoc,  1908,  673. 
Slyke,  Van,  and  Meyer,  G.  M.:  The  Amino-acid  Nitrogen  of  the  Blood. 

Preliminary   Experiments   on   Protein   Assimilation,    Jour.   Biol. 

Chem.,  vol.  xii,  Sept.,  1912. 
Smith  and  Candler:  On  the  Wassermann  Reaction  in  General  Paralysis 

of  the  Insane,  Brit.  Med.  Jour.,  1909,  199. 
Soltmann:  The  Chemistry  of  Cerebrospinal  Fluid,  Jour.  Amer.  Med. 

Assoc,  June  6,  1903. 
Stern,  Samuel:  The  Value  of  the  Noguchi  Butyric  Acid  Reaction  in 

Syphilis  and  Parasyphilitic  Affections,  Proc   Path.   Soc,  Phila., 

1910,  39. 
Swift,  Homer: 

A  Comparative  Study  of  Serum  Diagnosis  in  Syphilis,  Arch,  of 
Int.  Med.,  1909,  376. 

The  Use  of  Active  and  Inactive  Serum  in  Complement  Deviation 
Tests  for  Syphilis,  Arch,  of  Int.  Med.,  1909,  494. 

Anaphylaxis  to  Salvarsan,  Jour.  Amer.  Med.  Assoc,  Oct.  5,  1912. 

The  Intensive  Treatment  of  Syphilis,  Ibid. 

GERMAN  LITERATURE 

Sachs,  Hans: 

Antigene  tierischen  Ursprunges,  Kraus-Levaditi,   Handbuch  der 

Immunitaetsf.,  1908,  244-293. 
Spezifische   Bindung  und  Antikorper,  Oppenheimer's   Handbuch 
der  Biochemie  des  Menschen  und  der  Tiere,  G.  Fischer,  1909, 
275. 
Sachs  and  Altmann: 

Ueber  die  Wirkung  des  Oleinsaueren  Natrons  bei  W.  R.  auf  Syph- 
ilis, Berl.  klin.  Woch.,  1908,  494 
Einfluss   der   Reaktion   auf   das   Zustandekommen   der   Wasser- 
mannschen  Komplementbindung  bei  Syphilis,  Berl.  klin.  Woch., 
1908,  699. 
Sachs  and  Bolkowska:    Beitrage   zur  Kenntnis  der  komplexen  Kon- 
stitution  der  Komplemente,  Zeitschr.  f.  Immunitaetsf.,  1910,  776. 
Sachs  and  Rondoni: 

Theorie  und  Praxis  der  Wassermannschen  Syphilisreaktion,  Berl. 

klin.  Woch.,  1908,  xlv. 
Same  title,  Zeitschr.  f.  Immunitaetsf.,  1908-9,  p.  132. 
Salomon,  Oscar:  Beitrage  zur  Behandlung  der  Syphilis  mit  Ehrlich- 

Hata  606,  Med.  Klin.,  1910,  1652. 
Samele:    Beitrage    zur    Kenntniss  der   Cytologie  der   Cerebrospinal- 
fluessigkeit  bei  Nervenkrankheiten,  Zeitschr.  f.  klin.  Med.,  1906, 
p.  262. 
Sarbo:  Ueber  atypischen  Ausfall  der  W.  R.  bei  einem  Fall  von  anato- 
misch  sicherer  Paralyse,  Monatschr.  u.  Neurol.,  22. 


LITERATURE  323 

Satta  and  Donati: 

Ueber  das  Verhalten  von  verschiedenen  Extrakten  bei  der  W.  li- 
mit Beruecksichtigung  ihrer  antikomplementaeren  und  hemo- 
lytischen  Wirkung,  Wien.  klin.  Woch.,  1910,  659. 
Ueber  die  Hemmung  der  W.  R.  durch  Sublimat  und  ueber  die 
Moeglichkeit  dieselbe  aufzuheben,  Miinch.  med.  Woch.,  1910, 
567. 
Hat  das  Sublimat  eine  Wirkung  auf  die  W.  R.,  Wien.  klin.  Woch., 

1910,  739. 
Ueber  den  Einfluss  des  Alkohols  auf  luetische  Sera  bei  der  Komple- 
mentbindungsreaktion,  Ibid.,  1910,  1074. 
Schaef er :  Ueber  das  Verhalten  der  Cerebrospinalfluessigkeit  bei  gewissen 

Geisteskrankheiten,  Neurol.  Centralbl.,  1901,  p.  1066. 
Schatiloff  and  Isabolinsky:  Untersuchungen  ueber  die  Wassermann- 
Neisser-Brucksche  Reaktion  bei  Syphilis,   Zeitschr.   f.   Immuni- 
taetsf.,  1909,  316. 
Scheidemantel:  Erfahrungen  ueber  die  Spezificitaet  der  W.  R.:  Die 
Bewertung   und    Entstehung   inkompletter    Hemmungen,    Deut. 
Arch.  f.  klin.  Med.,  1911,  Bd.  101. 
Schereschewsky :   Ueber   Serumreaktion   bei   Scharlach   und   Masern, 

Munch,  med.  Woch.,  1908,  794. 
Schleier,  F.: 

Zur  Frage  der  Komplementbindung,  Deut.  med.  Woch.,  1908,  p. 

1373. 
Zur  Frage  der  Komplementbindung  bei  Scharlach,   Wien.  klin. 
Woch.,  1908,  p.  1373. 
Schlesinger:  Cytologische  Untersuchungen  des  Liquor  cerebrospinalis, 

Deut.  med.  Woch.,  1904. 
Schnitzler:    Zur   differentialdiagnostischen    Beurteilung   der   isolierten 
"Phase  I"  reaction  in  der  Spinalfluessigkeit,  Zeitschr.  f.  d.  ges. 
Neur.  u.  Psych.,  1911,  p.  210. 
Schoenborn:  Bericht  ueber  Lumbalpunktionen  an  230  Nervenkranken, 
mit  besonderer  Beruecksichtigung  der  Cytodiagnose,  Med.  Klinik, 
1906,  Nos.  23  and  24. 
Schoo,  H.  T.  M.:  Ueber  positive  Reaktion  von  Wassermann  bei  Malaria, 

Nederl.  Tydschr.  v.  Geneeskunde,  1910,  No.  5. 
Schottmueller: 

Der  Liquor  cerebrospinalis  insbesondere  im  Zusammenhange  mit 
der  W.  R.  bei  Poliomyelitis  acuta  epidemica,  Miinch.  med.  Woch., 
1912,  p.  1988. 
Meningitis    cerebrospinalis    epidemica    (Weichselbaum), ,  Miinch. 
med.  Woch.,  1905. 
Schottmueller  and  Schumm:  Nachweis  von  Alkohol  in  der  Spinal- 
fluessigkeit von  Saeufern,  Neurol.  Centralbl.,  1912,  No.  31. 
Schreiber  and  Hoppe:  Ueber  die  Behandlung  der  Syphilis  mit  dem 
neuen  Ehrlich-Hataschen  Arsenpraeparat,  No.  606,  Miinch.  med. 
Woch.,  1910,  1430. 


324      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

Schuermann:  Luesnachweis  durch  Farbenreaktion,  Deut.  med.  Woch., 

1909,  616. 
Schuermann,  W.:  Ein  kuenstlicher  Extrakt  zur  Anstellung  der  Lues- 

reaktion,  Med.  Klin.,  1909,  627. 
Schuetze:  Tabes  und  Lues,  Zeitschr.  f.  klin.  Med.,  1908,  pp.  397^24. 
Schuetze,  A.:   Experimentelle  Beitrage   zur   Wassermannschen  Sero- 

diagnostik  bei  Lues,  Berl.  klin.  Woch.,  1907,  126. 
Schultz-Zehden:   Erfahrungen  ueber  die   Dungernsche   Methode  der 

Syphilisreaktion  in  der  Sprechstunde,  Med.  Khn.,  1910,  1058. 
Schwartz,  W.,  and  Flemming:  Ueber  das  Verhalten  des  Ehrlich-Hatas- 

chen  Praeparates,  des  Arsenophenylglycin,  des  Jodkali  und  des 

Sublimats  zur  W.  R.,  Miinch.  med.  Woch.,  1910,  1933. 
Schwarz:  Ueber  Tabes  und  Lues  Cerebri  und  ihre  Beeinflussung  durch 

Salvarsan,  Petersburger  med.  Woch.,  1911,  49. 
Seligmann,  E.:  Zur  Kenntnis  der  W.  R.,  Zeitschr.  f.  Immunitaetsf., 

1909,  340. 
Seligmann  and  Blume:  Die  Luesreaktion  an  der  Leiche,  Berl.  klin. 

Woch.,  1909,  1116. 
Seligmann  and  Klopstock:  Serumreaktion  bei  Scharlach,  Berl.  klin. 

Woch.,  1908,  1719. 
Seligmann  and  Pinkus:  Beitrage  zur  Theorie  und  Praxis  der  W.  R., 

Zeitschr.  f.  Immunitaetsforschung,  1910,  377. 
Siemerling:  Ueber  den  Wert  der  Untersuchung  des  Liquor  cerebro- 

spinalis  fuer  die   Diagnose  der   Nerven  un   Geisteskrankheiten, 

Berl.  klin.  Woch.,  1904,  No.  21;  1909,  No.  21. 
Silberberg:  Ueber  Befunde  der  Eberth-Gaffkyschen  Bacillen  in  der 

Cerebrospinalfluessigkeit    bei    Typhus    abdominalis,    Berl.    khn. 

Woch.,  1908,  1354. 
Simon:   Zur   Untersuchung   des   Liquor   cerebrospinalis,    Wien.   khn. 

Woch.,  1911,  No.  24. 
Skoczynski:   Chemische   Untersuchung   der   Cerebrospinalfluessigkeit, 

Ref.  Neurol.  Centralbl.,  1905,  No.  1. 
Slawyk:  Ein  Fall  von  Allgemeininfektion  und  Influenzabacillen,  Zeit- 
schr. f.  Hyg.,  1899,  No.  32. 
Sleeswijk,  J.  G.:  Die  Serodiagnostik  der  Syphihs  nach  Noguchi,  Deut. 

med.  Woch.,  1910,  1213. 
Sly ke, Van:  Die gasometrische  Bestimmung  von  primaerem  aliphatischen 

Aminostickstoff  und  ihre  Anwendung  auf  physiologisch-chemis- 

chem   Gebiete,    Handbuch   der   biochemischen   Arbeitsmethoden 

Urban  and  Schwarzenberg,  Berlin,  1912. 
Smidt:  Ueber  Eiweissreaktion  in  der  Cerebrospinalfluessigkeit  Gesun- 

der,  Geistes  und  Nervenkranker,  These,  June,  1909. 
Sobernheim,  W. : 

Wassermannschekomplementbindungsmethode  und  Ozaena,  Arch, 
f.  Laryngol.,  1909,  xxii,  1. 

Ozaena  und  Syphilis,  Zeitschr.  f.  Laryngol.,  1909,  430. 


LITERATURE  325 

Sober nheim,  W.:   Zur  Organisation  der  Serodiagnostik  nach  Wasser- 

mann,  Berl.  klin.  Woch.,  1910,  1365. 
Spaet,  W.:  Ueber  den  Mechanismus  der  W.  R.,  Folia  Serol.,  1910,  v. 
Spielmeyer:  Schlafkrankheit  und  progressive  Paralyse,  Munch,  med. 

Woch.,  1907,  No.  22. 
Spiethoff:  Salvarsan  und  Nervensystem,  Miinch.  med.  Woch.,  1912,  p. 

1087. 
Spiethoff,  Bodo:  Arsenobenzol  bei  Syphilis,  Miinch.  med.  Woch.,  1910, 

1822. 
Spina: 

Experimentelle   Untersuchungen   ueber   die   Bildung   des   Liquor 

cerebrospinal,  Arch.  f.  d.  ges.  Physiol.,  1899,  p.  204. 
Ueber  den  Einfluss  des  hohen  Blutdruckes  auf  die  Neubildung  der 
Cerebrospinalfluessigkeit,  Ibid.,  1900,  p.  80. 
Staeubil:  Meningismus  typhosus  und  meningotyphus,  Duet.  Arch.  f. 

klin.  Med.,  1905,  Bd.  82. 
Stanek:  Ueber  die  Cholin  Salze,  Zeitschr.  f.  phys.  Chem.,  1905,  p. 

448. 
Steffenhagen:  Ueber  Komplementbindungsreaktion  bei  Lepra,   Berl. 

klin.  Woch.,  1910,  1363. 
Stern,  Carl: 

Ueber  die  sogenannte  "Verfeinerungen"  der  W.  R.,  Deut.  med. 

Woch.,  1910,  1118. 
Ueber  den  Einfluss  der  Zittmannschen  Kur  auf  den  Ausfall  der 
W.  R.,  Med.  klin.,  1910,  898. 
Stern,  Margar: 

Zur  Technik  der  Serodiagnostik  der  Syphilis,  Berl.  klin.  Woch., 

1908,  1489. 
Eine    Vereinfachung    und    Verfeinerung    der    serodiagnostischen 

Syphilisreaktion,  Zeitschr.  f.  Immunitaetsf.,  1909,  422. 
Ueber  die  Bewertung  der  unsicheren  und  paradoxen  Reaktionen 
bei  der  serodiagnostischen   Untersuchung  der  Syphilis,   Ibid., 
1910,  201. 
Stertz : 

Die  Serumdiagnostik  in  der  Psychiatrie  und  Neurologie,  Allge- 

meine  Zeitschr.  f.  Psych,  u.  psych,  gericht.  Med.,  1908,  565. 
Die  Serodiagnostik  in  der  Psychiatrie  und  Neurologie,  Allgemeine 

Zeitschrift  f.  Psychiatrie,  1908,  p.  665. 
Die  Bedeutung  der  Lumbalpunktion  fuer  die  Diagnose  von  Gehirn 
und  Rueckenmarkskrankheiten,  Med.  Klin.,  1912,  p.  133. 
Strauss:  Die  diagnostische  Bedeutung  der  Punktion  des  Wirbelkanals, 

Deut.  Arch.  f.  klin.  Med.,  1896,  Bd.  57. 
Stuehmer : 

Typhusbacillen    in   der   Cerebrospinalfluessigkeit,    Miinch.    med. 

Woch.,  1911,  No.  7. 
Zur  Technik  der  Untersuchung  der  Lumbalfluessigkeit  auf  W.  R., 
Zentralbl.  f.  Bacter.,  1911,  p.  171. 


326      SEROLOGY  OF   NERVOUS    AND   MENTAL  DISEASES 

Stuemer,  A.:  Ueber  die  Verwendung  autolisierter  Lebern  zu  Organex- 

trakten  fuer  die  W.  R.,  Zentralbl.  inn.  Med.,  1910,  No.  14. 
Stuempke,  G.:  Welche  Beziehungen  bestehen  zwischen  Jd*d  (Jodkali) 
und  dem  Ausfall  der  Seroreaktion,  Munch,  med.  Woch.,  1910,  1532. 
Sugai:    Zur    klinisch-diagnostischen    Verwertung    der    Komplement- 
bindunsmethode  bei  lepra,  Arch,  f .  Dermat.  u.  Syph.,  1909,  313-319. 
Swift,  Homer,  and  Ellis,  W.  M.:  Die  kombinierte  lokal  und  AHgemein- 
behandlung  der  Syphilis  des  Zentralnervensystems,  Miinch.  med. 
Woch.,  Nos.  36  and  37,  1913. 
Szesci : 

Beitrage  zur  Differentialdiagnose  der  Dementia  paralytica,  Sclero- 
sis multiplex  und  Lues  cerebrospinalis,  Monatschr.  f.  Psychiat- 
rie,  Sept.,  1910,  No.  26. 
Neue  Beitrage  zur  Cytologie  des  Liquor  cerebrospinalis,  Ueber 
Art  und  Herkunft  der  Zellen,  Zeitschr.  f.  d.  ges.  Psych,  u. 
Neurol.,  1911,  No.  6. 
Weitere  Beitrage  zur  Cytologie  des  Liquor  cerebrospinalis.     Ueber 

die  sogenannte  Degeneration  der  Zellen,  Ibid.,  1912,  No.  9. 
Ueber   das  Vorkommen   von  peptolytischen   Fermenten   in   der 

Lumb%lfluessigkeit,  Wien.  klin.  Woch.,  1911,  No.  33. 
Zur   Technik   der   chemischen   und   cytologischen   Untersuchung 
der  Lumbalfluessigkeit,  Monatschr.  f.  Psych,  u.  Neurol.,  1910, 
p.  152. 

FRENCH  LITERATURE 
Sabrazes: 

Note  sur  le  point  de  congelation.  Examen  cytologique  des  liquides 
du  d'hydrorrhee  nasale,  Gaz.  des  sciences  med.  de  Bordeaux, 
Jan.  25,  1903. 
Presence  de  serine  dans  le  liquide  C.  R.  normal,  Gaz.  hebd.  de 

sciences  med.  de  Bordeaux,  Aug.  2,  1903,  p.  376. 
La  ponction  lombaire,  Gaz.  hebd.  des  Scien.  med.  de  Bordeaux, 
July  22,  1906,  p.  339. 
Salebert  and  Louis:  Cytologie  du  liquide  C.  R.  dans  la  meningite  cerebro- 
spinale.  Role  phagocytaire  cellules  endothelials,  C.  R.  Soc.  Biol., 
1909,  p.  770. 
Sappey:  Les  therapeutiques  rachidiennes  du  tabes;  L'Electro-mercurol. 
Considerations  sur  son  mode  d' action,  These  Montpelher,  1910. 
Schaeffer,  G.:  La  choline.  Etude  chimique  et  physiologique  de  cette 

substance,  Biologie  med.  (F.  Billon),  Oct.,  1909,  p.  309. 
Schmiergeld:  Etude  sur  la  poliomyelite  anterieure  de  l'adulte,  Paris, 

Jules  Rousset,  1907. 
Sezary  and  Palliard:  Constatation  de  treponeme  dans  le  liquide  C.  R., 

C.  R.  Soc.  Biol.,  1910,  p.  295. 
Sicard: 

'  Le  liquide  C.  R.,  Masson  &  Co.,  Paris,  1902. 
Les  injections  sous-arachnoidiennes  et  le  liquide  C.  R.  Recherches 
experimentales  et  cliniques,  These  de  Paris,  1899,  No.  124. 


LITERATURE  327 

Sicard: 

Permeabilite  meningee,  C.  R.  Soc.  Biol.,  1902,  p.  1356. 
Chromodiagnostic   du   liquide    C.    R.    Hemorragies   du   nevraxe, 

meningites,  ictere,  Presse  med.,  Jan.  25,  1902. 
Glycometrie   du   liquide   C.   R.,   Acad,   de   Medecine,    Oct.    18, 

1904. 
Nevralgie  du  trijumeau  et  ponction  lombarie,  C.  R.  Soc.  Biol., 

1904,  p.  357. 
Traitement  par  les  injections  arachnoidiennes  lombaires  de  cer- 
tains symptomes  du  tabes  inferieur,  C.  R.  Soc.  Biol.,  1910,  p. 
1105. 
Sicard  and  Bloch: 

Permeabilite  meningee  a  l'arsenobenzol,  C.  R.  Soc.  Biol.,  1910, 

p.  624;  Soc.  med.  des  Hop.,  Nov.  18,  p.  479. 
Variations  quantitatives  de  la  lymphocytose  rachidienne  chez  les 
tab6tiques  non  traites.   Influence  de  la  statique.   Deductions 
pathogeniques,  Soc.  med.  des  Hop.,  July  7,  1911. 
Sicard  and  Brecy: 

Meningite    cerebrc-spinale    ambulatoire  curable.   Cytologie,  Soc. 

med.  Hop.,  April,  1901,  p.  369. 
Chromodiagnostic  dans  l'hemorragie  meningee,  C.  R.  Soc.  Biol., 
Nov.,  1901,  p.  1050. 
Sicard  and  Descomps:  Syndrome  de  coagulation  massive  de  xantho- 
chromie  et  d'hemato-lymphocytose  du  liquide  C.  R.,  Gaz.  des  Hop., 
Oct.,  1908. 
Sicard  and  Foix: 

Les  reactions  du  liquide  C.  R.   au  cours  des  pachymeningites 

rachidiennes,  Soc.  de  Neurol,  de  Paris,  No.  10,  p.  636,  1910. 
Glucose  rachidien  et  septicite,  Soc.  de  Neurol.,  March,  1911. 
Sicard  and  Gy:  Meningite  sarcomateuse  a,  predominance  bulbo-pro- 
tuberantielle.     Cytodiagnostic.     Reaction     neoplastique,     Revue 
Neurologique,  Dec.  15,  1908. 
Sicard  and  Rousseau  Langwelt:  Glycometrie  du  liquide  C.  R.  chez 
1' enfant.     Sa  valeur  dans  le  diagnostic  des  meninges  aigues,  Soc. 
med.  des  Hop.,  Oct.  14,  1904. 
Sicard   and  Salin:   Reactions  meningees   consecutives   aux  injections 
sous-arachnoidiennes  lombaires  du  serum  du  cheval  et  de  serum 
artificiel,  C.  R.  Soc.  Biol.,  1910,  523. 
Sicard,  Guillain,  and  Ravaut:  Chimie  du  liquide  C.  R.,  Archives  de 

Neurologie,  1903,  p.  472. 
Slatineanu  and  Danielopolu: 

Fixation  de  l'alexine  essayee  avec  le  serum  et  le  liquide  cephalo- 
rachidien  des  lepreux,  en  presence  de  la  lecithine  comme  antigene, 
C.  R.  Soc.  Biol.,  1909,  332. 
Reaction  de  fixation  avec  le  serum  et  le  liquide  cephalo-rachidien 
des  malades  de  lepre  en  presence  de  l'antigene  syphilitique, 
Centralbl.  f.  Bakt.,  etc.,  Orig.  1,  Abteil,  1909,  289. 


328      SEROLOGY  OF   NERVOUS    AND   MENTAL   DISEASES 

Slatineanu  and  Galesesco:  Recherches  cytologiques  sur  le  liquide  C.  R. 

dans  le  typhus  exanthematique,  C.  R.  Soc.  Biol.,  No.  61,  p.  230. 
Souques  and  Aynaud:  Passage  de  1' acetone  dans  le  liquide  C.  R.  au 

cours  du  coma  diabetique  chez  l'homme  et  a  l'etat  normal  chez 

les  animaux,  Soc.  med.  des  Hop.,  Jan.  25,  1907. 
Subsol:  Etude  de  liquide  C.  R.  dans  l'epilepsie  essentielle,  These  de 

Paris,  1903,  No.  308. 

ITALIAN  LITERATURE 

Serra,  Alberto:  La  sierodiagnosi  di  Wassermann  nella  lepra,  Policlin. 

Sez.  med.,  1909,  545. 
Sorrentino:    Suh"    importanza  della   citoscopia   cefalo-rachidiana   nei 

sifihtici,  Rif.  med.,  1911,  p.  49. 

T 
ENGLISH  LITERATURE 

Thomson,  Hill,  and  Halliburton:  Observations  on  the  Cerebrospinal 
Fluid  in  the  Human  Subject,  Lancet,  1899,  No.  9. 

Turner :  Examination  of  the  Cerebrospinal  Fluid  as  an  Aid  to  Diagnosis 
in  Certain  Cases  of  Insanity,  etc.,  Jour,  of  Ment.  Sci.,  1910,  485. 

GERMAN  LITERATURE 

Taege:  Die  Technik  der  Wassermannschen  Serodiagnostik  der  Syphilis, 

Munch.  Med.  Woch.,  1908,  1730. 
Tedeschi:  Ueber  Cuti  und  Ophthalmoreaktion  bei  Syphilis,  Munch. 

med.  Woch.,  1908,  2200. 
Thomsen,  O.:  Die  Bedeutung  der  positiven  W.  R.  mit  Frauenmilch 

fuer  die  Wahl  einer  Amme,  Berl.  klin.  Woch.,  1910,  1748. 
Thomsen  and  Boas,  Ismar:  Die  W.  R.  bei  congenitaler  Syphilis,  Berl. 

klin.  Woch.,  1909,  539. 
Tobler:  Ueber  die  Lymphocytose  der  Cerebrospinalfluessigkeit  bei  kon- 

genitaler  Syphilis  und  ihre  diagnostische  Bedeutung,  Jahrbuch  f . 

Kinderheilkunde,  1906,  p.  64. 
Tomasczewski : 

Ueber  eine  einfache  Methode  bei  Kanienchen  Primaeraffekte  zu 
erzeugen,  Deut.  med.  Woch.,  1910,  1025. 

Untersuchungen  ueber  die  Wirkung  des  Hg.  und  Jods  bei  der 
experimentellen  Syphilis,  Ibid.,  1910,  653. 
Torday,   A.   von:   Bericht  ueber  die  Ehrlich-Hatasche   Behandlung, 

Wien.  klin.  Woch.,  1910,  1381. 
Toyosumi : 

Welche   Antikoerper   spielen   bei   der   Komplementbindung   eine 
Rolle,  Arch.  f.  Hyg.,  1909,  No.  1. 


LITERATURE  329 

Toyoeumi: 

Ueber  die  Natur  der  Komplementbindenden  Stoffe  bei  Lues,  Wien. 

klin.  Woch.,  1909,  747. 
Komplementabsorption    durch    Bakterienextrakte,    Zentralbl.    f. 

Bakt.,  Abteil  1,  1909,  325. 
Ueber  die  Komplementbindenden  Stoffe  Luetischer  Sera,  Ibid., 
1909,  601. 
Trembur:  Die  Quinckesche  Lumbalpunktion  bei  der  Erkennung  der 

Meningitis  tuberculosa,  etc.,  Klin.  Jahrbuch,  1911,  p.  360. 
Treupel,  G.:  Weitere  Erfahrungen  bei  syphilitischen  para  und  meta 
syphilitischen  Erkrankungen  mit  Ehrlich-Hata  Injektionen,  Deut. 
med.  Woch.,  1910,  1787. 
Tschernogubof : 

Einfache   Methode  der  Serumdiagnose  bei  Syphilis,   Berl.   klin. 

Woch.,  1908,  2107. 
Zur  Frage  der  Herstellung  von  syphilitischen  Antigenen,  Wien. 

klin.  Woch.,  1906,  336. 
Ein  vereinfachtes  Verfahren  der  Serumdiagnose  bei  Syphilis,  Deut. 
med.  Woch.,  1909,  668. 

FRENCH  LITERATURE 

Tedeschi:  Syndrome  de  la  queue  de  cheval,  Gazetta  degli  Ospedali  e 

delle  Cliniche,  Aug.,  1906. 
Tesson:  Contribution  a  1' etude  de  la  ponction  lombaire  dans  les  frac- 
tures du  crane,  Gaz.  des  Hop.,  April  22,  1901,  p.  921. 
Thiery,  P.:  De  la  presence  du  sucre  dans  le  liquide  hydrocephalique, 

Prog,  med.,  1886,  p.  286. 
Tuffier  and  Milian: 

Pronostic  des  fractures  du  crane  par  la  ponction  lombaire,  C.  R. 

Soc.  Anat.,  June  5,  1901. 
La  ponction  lombaire  dans  les  fractures  du  crane,  C.  R.  Soc.  Biol., 

May,  25,  1901;  Soc.  med.  des  Hop.,  July  12,  1901. 
Diagnostic  des  fractures  du  crane  par  la  ponction  lombaire,  Soc. 

med.  des  Hop.,  July  12,  1902. 
H6morragies  intra-craniennes,  Presse  m6d.,  March  5,  1902. 
La  xanthochromic  du  liquide  C.  R.  Fracture  du  crane  chez  un 
alcoolique,  Bull,  de  la  Soc.  Anat.,  May  16,  1902,  p.  489. 

U 

GERMAN  LITERATURE 
Uhlenhuth:  Komplementbindung  und  Bluteiweisdifferenzierung,  Deut. 

med.  Woch.,  1906,  p.  1244. 
Uhlenhuth  and  Muelzer:  Die  experimentellen  Grundlagen  chemothera- 

peutischer  Versuche  mit  neueren  Arsenpraeparaten  bei  Spirochae- 

tenkrankheiten   mit   besonderer   Beruecksichtigung   der   Syphilis, 

Deut.  med.  Woch.,  1910,  1262. 


330      SEROLOGY    OF   NERVOUS    AND    MENTAL   DISEASES 

V 
FRENCH  LITERATURE 

Vigneras:  Hemorragie  meningo-spinale,  These  de  Paris,  1903. 

Villaret  and  Tixier: 

Dissociation  des  reactions  cliniques,  eytologiques,  bacteriologiques 
et   anatomo-pathologiques   dans  certains  formes   de    meningite 
tuberculeuse,  C.  R.  Soc.  Biol.,  Nov.,  1905. 
Eclampsie  puerperale  et  leucocytose  du  liquide  C.  R.,  C.  R.  Soc. 
Biol.,  1907,  p.  1042. 

Vincent:  Deux  cas  de  meningite  chronique  syphilitique,  Rev.  neurol., 
1908,  p.  1050. 

Vincent  and  Combe:  Contribution  au  diagnostic  de  la  meningite  tuber- 
culeuse, C.  R.  Soc.  Biol.,  1909,  p.  465. 

Viteman:  Le  regime  dechlorure  dans  l'epilepsie,  These  de  Paris,  June 
14,  1906,  Xo.  315. 

Voisin,  J.  and  R.:  Le  liquide  C.  R.  dans  Fepilepsie  essentielle,  Soc.  med. 
des  Hop.,  March  IS,  1910,  p.  282. 

Voisin,  R.:  Les  meninges  au  cours  des  infections  aigues  de  l'appareil 
respitatoire;  broncho-pneumonie  et  pneumonie,  These  de  Paris, 
Feb.,  1904,  Xo.  203. 

Voisin  and  Paisseau:  Les  reactions  meningees  au  cours  des  encephalo- 
pathies chroniques  de  1' enfant,  Arch,  de  Med.  des  enfants,  Xo.  4, 
1910. 

Voulcoff :  Contribution  a  l'etude  du  liquide  C.  R.  dans  les  P.  G.,  These 
de  Montpelher,  March,  1904,  Xo.  6. 

W 

EXGLISH  LITERATURE 

Walker  and  Swift :  A  Study  of  the  Addition  of  Cholesterin  to  the  Alco- 
holic Extracts  of  Tissues  Used  for  Antigens  in  the  Wassermann 
Reaction,  Jour.  Exp.  Med.,  vol.  xviii.  Xo.  1.  1913. 

Waugh,  J.  F.:  Results  of  Experience  with  Xoguchi  Modification  of  the 
Wassermann  Serodiagnosis  Test  for  Syphilis,  Jour.  Amer.  Med. 
Assoc,  1919,  844. 

Weil.  Richard:  On  the  Resistance  of  Human  Erythrocytes  to  Cobra 
Venom.  Jour.  Infect.  Dis.,  1909,  688. 

Wieder  and  LEngle:  Some  Studies  of  the  Precipitin  Tests  for  Syphilis, 
Jour.  Amer.  Med.  Assoc,  1909,  1535. 

Williamson: 

The  Cerebrospinal   Fluid   in   General   Paralysis   and   in  Xervous 

Lues,  Lancet,  1909,  1047. 
The  Bacillus  Paralyticus,  Jour,  of  Ment.  Sci.,  1909,  642. 

Williamson  and  Phillips:  Further  Investigation  on  the  Cerebrospinal 
Fluid  in  Insanity,  Jour,  of  Ment.  Sci.,  1912,  p.  240. 


LITERATURE  331 

Wolbarst,   Abr.:   Contradictory  Findings  in  the  Wassermann   Test, 

N.  Y.  Med.  Jour.,  Feb.  22,  1913. 
Wolfsohn:  The  Cutaneous  Reaction  of  Syphilis,   Bull.   Johns  Hop. 

Hosp.,  1912,  p.  223. 
Wollstein:   Influenza   Meningitis   and   its   Experimental   Production, 

Amer.  Jour.  Dis.  of  Children,  1911,  p.  42. 
Wollstein  and  Lamar:  The  Presence  of  Antagonistic  Substances  in  the 

Blood-serum  in  Early  and  Late  Syphilis,  Paralysis,  and  Tabes, 

Arch,  of  Int.  Med.,  1908,  341. 
Wright,  H.  W.:  A  Consideration  of  Constitutional  Inferiority,  N.  Y. 

Med.  Jour.,  Dec.  26,  1908. 

GERMAN  LITERATURE 

Wada  and  Matsumoto:  Liquor  cerebrospinalis  bei  Geisteskrankehiten, 

Jahrbuch  f.  Psych.,  1910,  p.  153. 
Wagner:  Einige  Beobachtungen  ueber  den  Druck  im  Lumbalkanal, 

insbesondere  bei  Tabes  dorsalis,  Charite-Annalen,  1909,  No.  33. 
Walter:  Studien  ueber  den  Liquor  cerebro-spinalis,  Monatschr.  f.  Psych. 

und  Neurol.,  Sept.,  1910,  No.  28. 
Wassermaeyer  and  Bering:  Die  W.  R.  in  der  Psychiatrie  und  Neurologie 

mit  besonderer  Beruecksichtigung,  etc.,  Arch.  f.  Psych.,  1910,  p. 

822. 
Wassermann,  A.: 

Ueber  die  Entwicklung  und  den  gegenwertigen  Stand  der  Serc- 
diagnostik  gegenueber  Syphilis,  Berl.  klin.  Woch.,  1907,  1599, 
1634. 

Ueber  die  Serodianostik  der  Syphilis  und  ihre  praktische  Bedeu- 
tung  fuer  die  Medizin,  Wien.  klin.  Woch.,  1908,  745. 

Die  Diagnose  der  Syphilis  bei  Erkrankungen  des  Zentralnerven- 
systems,  Zentralbl.  f.  Nervenheilk.  u.  Psych.,  1908,  975. 
Wassermann  and  Meier:  Die  Serodiagnostik  der  Syphilis,  Munch,  med. 

Woch.,  1910,  No.  24. 
Wassermann    and    Plaut:    Ueber    das    Vorhandensein    syphilitischer 

Antistoffe  in  der  Cerebrospinalfluessigkeit  vqn  Paralytikern,  Deut. 

med.  Woch.,  1906,  1769. 
Wassermann  and  Schucht:  Nachweis  specifisch-luetischer  Substanzen 

durch  Komplementverankerung,  Zeitschr.  f.  Hyg.  u.  infektionskr., 

1906,  451. 
Wassermann,  Neisser,  and  Bruck:  Eine  Serodiagnostische  Reaktion  bei 

Syphilis,  Deut.  med.  Woch.,  1906,  745. 
Wassermann,  M.,  and  Meier:  Zur  klinischen  Verwertung  der  Sero- 
diagnostik bei  Lues,  Deut.  med.  Woch.,  1907,  1287. 
Wechselmann: 

Postkonzeptionelle  Syphilis  und  W.  R.,  Deut.  med.  Woch.,  1909, 
665. 

Beobachtungen  an  503  mit  Dioxy-diamido-arseno-benzol  behan- 
delten  Krankheitsfaellen,  Deut.  med.  Woch.,  1910,   1478. 


332      SEROLOGY    OF   NERVOUS   AND    MENTAL   DISEASES 

Wechselmann: 

Ueber  die  Behandlung  der  Syphilis  mit  606,  Berl.  klin.  Woch., 

1910,  126. 
Ueber  intravenoese  Injection  von  Neosalvarsan,  Berl.  klin.  Woch., 

1912,  p.  1446. 
Ueber  die  Wirkung  des   Salvarsans   auf  die  Cerebrospinalflues- 
sigkeit,  Berl.  klin.  Woch.,  1912,  p.  688. 
Wechselmann  and  Meier:  W.  R.  in  einem  Fall  von  Lepra,  Deut.  med. 

Woch.,  1908,  1314. 
Weidanz:  Die  W.  R.  bei  Anwendung  kleinster  Blutmengen,  Berl.  klin. 

Woch.,  1908,  2440. 
Weil,  E.,  and  Braun,  H.: 

Ueber  die  Entwicklung  der  Serodiagnostik  bei  Lues,  Wien.  klin. 

Woch.,  1908,  624. 
Ueber  Antikoerper  Befunde  bei  Lues,  Tabes  dorsalis,  und  Paralyse, 

Berl.  klin.  Woch.,  1907,  pp.  1517,  1570. 
Ueber  die  Rolle  der  Lipoide  bei  der  Reaktion  auf  Lues,  Wien. 

klin.  Woch.,  1908,  151. 
Ueber  positive  W.  R.  bei  nicht-luetischen  Erkrankungen,  Wien. 
klin.  Woch.,  1908,  938. 
Weil  and  Kafka: 

Ueber   die   Durchgaengigkeit   der   Meningen   besonders   bei   der 

progressiven  Paralyse,  Wien.  klin.  Woch.,  1911,  No.  26. 
Weitere  Untersuchungen  ueber  den  Haemolysingehalt  der  Cerebro- 
spinalfiuessigkeit  bei  akuter  Meningitis  und  progressiver  Par- 
alyse, Med.  klin.,  1911,  No.  34. 
Werther:  Ueber  das  Wesen  und  den  Wert  der  W.  R.  und  500  eigene 
Untersuchungen  mit  der  Hechtschen  Modinkation,  Monatschr.  f. 
prakt.  Dermat.,  1910,  147. 
Werther  and  Koenig:  Ueber  die  Hechtsche  Modifikation  der  W.  R. 
ueber  die  Erfahrungen  bei  500  Untersuchungen  und  ueber  den 
Wert  der  Reaktion  fuer  die  Praxis,  Munch,  med.  Woch.,  1910,  161. 
Weygandt:  Ueber  die  Frage  syphilitischer  Antistoffe  in  der  Cerebrospi- 
nalfluessigkeit  bei  Tabes  dorsalis,  Ref.  Munch,  med.  Woch.,  1907, 
p.  1557. 
Wolff,  Arthur:  Vergleichende  Untersuchungen  ueber  W.  R.,  Lympho- 
cytose  und  Globulinreaktion  bei  Erkrankungen  des  Nervensystems, 
Deut.  med.  Woch.,  1910,  748. 
Wolfssohn,  G.:  Ueber  W.  R.  und  Narkose,  Deut.  med.  Woch.,  1910,  505. 


FRENCH  LITERATURE 

Widal  and  Abrami:  Ictere  grave  infectieux  avec  retention  et  uremie 
seche  par  azotemie;  permeabilite  des  voies  biliaires.  Hyperplasie 
des  cellules  hepatiques,  Bull,  de  la  Soc.  med.  des  Hop.  de  Paris, 
Feb.,  1908. 


LITERATURE  333 

Widal  and  Foin:  Uree  dans  le  liquide  C.  R.,  C.  R.  Soc.   Biol.,  Oct., 

1904,  p.  282. 
Widal  and  Froin:  L'uree  dans  le  liquide  C.  R.  des  brightiques,  Gaz. 

des  Hop.,  Oct.  26,  1904,  p.  1182. 
Widal   and   Joltrain:   Biligenie   hemolytique   local   dans   l'hemorragie 

meningee,  C.  R.  Soc.  Biol.,  June  5,  1909,  p.  917. 
Widal  and  Sicard:  Etude  sur  le  sero-diagnostic  de  la  fievre  typhoid, 

Annales  de  1' Institute  Pasteur,  1897. 
Widal,  Lemierre,  and  Boidin:  Liquide  C.  R.,  puriforme  au  coursde  la 

syphilis   des   centres   nerveux;    integrite   des   polynucleares,    Soc. 

med.  des  Hop.,  June  22,  1906,  p.  645. 
Widal,  Sicard,  and  Ravaut: 

Cryoscopie  du  liquide  C.  R.  Application  al  'etude  des  meningites, 
C.  R.  Soc.  Biol.,  Nov.  2,  1900. 

Les  albumines  de  liquide  C.  R.  au  cours  de  certains  processus 
meninges  chroniques,  Rev.  neurol.,  April  2,  1903,  437. 

Cytologie  du  liquide  C.  R.  au  cours  de  quelques  processus  menin- 
gees  chroniques,  Gaz.  hebdom.  des  med.,  1901,  77. 

A  propos  de  cytodiagnostic  de  tabes,  Rev.  neurol.,  1903,  p.  289. 

Presence  d'un  pigment  derive  dans  le  liquide  C.  R.  au  cours  des 
icteres  chroniques,  C.  R.  Soc.  Biol.,  Feb.  8,  1902,  p.  159. 
Wilson:   Choline  signe  de  degenerescence  nerveuse,   son  importance 

clinique,  Soc.  Neurol.,  1904,  p.  401. 
Wolf:  Des  elements  de  diagnostic  tires  de  la  ponction  lombaire,  These 

de  Paris,  July  20,  1901,  No.  669. 


GERMAN  LITERATURE 

Zaloziecki: 

Zur   klinischen    Bewertung   der    serodiagnostischen   Luesreaktion 

nach  Wassermann  in  der  Psychiatrie,  Monatschr.  f.  Psych,  u. 

Neurol.,  Sept.,  1900. 
Liquor  Cerebrospinalis  und  Salvarsan,  Berl.  klin.  Woch.,  1912,  No. 

49. 
Ueber  den  Antikoerpernachweis  im  Liquor  cerebrospinalis,  seine 

theoretische  und  praktische  Bedeutung,  Munch.  Arch,  f .  Hygiene, 

1913,  Bd.  80. 
Zur  Frage-  der  Permeabilitaet  der  Meningen,  Leipzig,  Vogel,  1913. 
Bemerkungen  zu  J.  Portmann's  Notiz;  Eine  neue  Modifikation  der 
,  W.  R.,  Berl.  klin.  Woch.,  1913,  No.  5. 
Ueber    den    Eiweisgehalt    der    Cerebrospinalfluessigkeit,    Deut. 

Zeitschr.  f.  Nervenheilk.,  1913,  Bd.  47,  48. 
Ueber  <rEigenloesende"  Eigenschaften  des  Meerschweinchenserums 

und  dadurch  bedingte  Fehlerquellen  der  W.  R.,  Deut.  med. 

Woch.,  1913,  No.  17. 


334      SEROLOGY   OF   NERVOUS   AND   MENTAL   DISEASES 

Zeissl:   Meine  bisherigen  Erfarungen  mit  Ehrlich   606,   Wien.   med. 

Woch.,  1910,  1865. 
Zeissler: 

W.  R.  bei  Scharlach,  Berl.  klin.  Woch.,  1908,  1887. 

Komplementschaedigung  durch  Schuetteln,   Ibid.,   1909,  2340. 

Quantitative  Hem m ungskoerperbestimmung  bei  der  W.  R.,  Ibid., 
1909,  1968;  1910,  968. 
Zradek:  Einige  Beitrage  zur  Kenntnis  der  Cerebrospinalfluessigkeit, 

Zeitschr.  f.  Phys.  Chem.,  1902,  No.  291. 
Zuelchaur:  Die  Serodiagnose  der  Dementia  paralytika,  Inaug.  Diss., 

Leipzig,  1910. 
Zweifel:  Zur  Aufklaerung  der  Eklampsie,  Arch.  f.  Gynaekol.,  1905,  76. 

ITALIAN,  GREEK,  AND  FRENCH  LITERATURE 

Zaccaria:  Ricerche  sulla  quantita  di  calcio  contenuta  nel  liquido  C.  R. 
di  bambibi  ammalati,  Clinica  Ital.  med.,  1906,  p.  813,  No.  12. 

Zilanakis: 

Intoxication  par  l'atropine,  Rev.  Neurol.,  1907,  p.  20. 
Contribution  a  l'etude  du  liquide  C.  R.  chez  les  alienes.  Statis- 
tique  et  conclusions  de  160  ponctions,  Rev.  Neur.,  1907,  p.  20. 

Ziveri,  A.:  Modification  de  la  methode  de  recherche  de  la  choline  et 
nouveUes  investigations  sur  sa  presence  et  la  presence  de  la  leci- 
thine  dans  le  liquide  C.  R.,  Revista  de  pathologia  nervosa  e  men- 
tale,  vol.  xiv,  p.  134,  March,  1909. 


INDEX 


Abscess,  cerebral,  98 

of  brain,  98 
Acellular    type    of    cerebrospinal 

syphilis,  159,  170 
Acetone  insoluble  antigen,  Nogu- 

chi's  method  of  preparing,  69 
Acid,  asparaginic,  254 

dichlorphenylarsenious,  204 
glutaminic,  254 
Acids,  amino-,  253 
Acromegaly,  116 
Acroparesthesia,  116 
Addison's  disease,  117 
Alanin,  253 
Alcoholic  neuritis,  109 
psychosis,   general  paresis  and, 

differentiation,  197 
tissue  antigens  for  Wassermann 
reaction,  69 
Alcoholism,  acute,  123 

chronic,  124 
Alzheimer's   method   of   counting 
cells  in  cerebrospinal  fluid,  39 
plasma    cells    in    cerebrospinal 
fluid,  35 
Amaurotic  family  idiocy,  99 
Amboceptor,  anti-sheep,  standard- 
ization of,  62 
together  with  antigen  and 
normal  serum,  63 
hemolytic,  for  Wassermann  re- 
action, preparation  and 
properties,  59 
standardization  of,  62 
low-power,  64 
Amidophenylarsenoxid,  205 
Amino-acids,  253 


Aminc-nitrogen  content  of    leutic 
sera,  261 
of  non-leutic  serum,  262 
of  serum,  253 
preparation  of  apparatus  for 

use,  255 
rationale,  253 
technic,  255 
testing  for,  258 
Amyotrophic  lateral  sclerosis,  104 
Aneurysm,  aortic,  as  contraindica- 
tion to  use  of  salvarsan,  234 
Antibodies,  47 
Antigen,  47 

acetone     insoluble,      Noguchi's 

method  of  preparing,  69 
alcoholic  tissue,  for  Wassermann 

reaction,  69 
in  Wassermann  reaction,  inhib- 
itory substances  used  as, 
72 
preparation  and  properties, 

65 
standardization   of   an   ex- 
tract to  be  used  as,  71 
Anti-sheep  amboceptor,  standard- 
ization, 62 
together  with  antigen  and 
normal  serum,  63 
Anxiety  depression,  123 

neuroses,  113 
Aortic  aneurysm  as  contraindica- 
tion to  use  of  salvarsan,  234 
Arsacetin  in  syphilis,  202 
Arsenic,  detection  of,  236 
biologic  test  for,  236 
Marsh  test  for,  237 

335 


336 


INDEX 


Arsenic  in  cerebrospinal  fluid,  32 
intolerance,     reaction     due     to, 
Herxheimer  reaction  and,  dif- 
ferentiation, 252 
Arsenophenol,  203 
Arsenophenylglycin,  202 
Asparaginic  acid,  254 
Ataxia,  hereditary,  102 
locomotor,  132.     See  also  Tabes 
dorsalis. 
Atoxyl,  201 

in  syphilis,  201 
Atrophy,  progressive  muscular,  105 
neurospinal  form,  105 
spinal  form,  104 
Atropin  intoxication,  131 

Bacilli,  tubercle,  in  cerebrospinal 
fluid,  search  for,  45 

Bacteriology  of  cerebrospinal  fluid, 
44 

Bauer's    modification    of    Wasser- 
mann  reaction,  73 

Biologic  test  for  detection  of  ar- 
senic, 236 

Blood,   collection  of,  for  Wasser- 
mann  test,  53 
in  cerebrospinal  fluid,  18 

Blood-taking,  technic  of,  50-53 

Boas'  modification  of  Wassermann 
reaction,  74 

Bordet-Gengou  phenomenon,  47 

Brain,  abscess  of,  98 
diseases  of,  95 

organic,  psychoses  accompany- 
ing, 122 
softening  of,  98 
syphilis  of,  170 
tumor  of,  96 

Brezovsky  and  Detre's  modifica- 
tion of  Wassermann  reaction,  74 

Browning's  modification  of  Wasser- 
mann reaction,  74 

Carbon  monoxid  intoxication,  131 
Cauda  equina,  diseases  of,  109 
Cells  in  cerebrospinal  fluid,  32 


Cells   in    cerebrospinal  fluid,   ab- 
normal count,  43 
Alzheimer's       method       of 

counting,  39 
French  method  of  counting, 

39 
Fuchs-Rosenthal     counting 

chamber  for,  41,  42 
in  disease,  33 
interpretation     of    findings 

after  counting,  43 
methods  of  counting,  39 
Nageotte's  counting  cham- 
ber for,  39,  40 
Nissl's  method  of  counting, 

39 
origin,  37 
plasma,  of  Alzheimer,  in  cerebro- 
spinal fluid,  35 
Cerebral  abscess,  98 
hemorrhage,  95 
softening,  98 
syphilis,  170 

endarteritic  form,  171 
general  paresis  and,  relation, 

171 
meningitic  form,  170 
thrombosis,  96 
tumor,  96 
Cerebrospinal    fluid,     Alzheimer's 
plasma  cells  in,  35 
anatomy,  18 
arsenic  in,  32 
bacteriology  of,  44 
blood  in,  18 
cells  in,  32 

abnormal  count,  43 
Alzheimer's       method       of 

counting,  39 
French  method  of  counting, 

39 
Fuchs-Rosenthal     chamber 

for,  41,  42 
in  disease,  33 
interpretation     of     findings 

after  counting,  43 
methods  of  counting,  39 


INDEX 


337 


Cerebrospinal  fluid,  cells  in,  Na- 
geotte's    counting  cham- 
ber for,  39,  40 
Nissl's  method  of  counting, 

39 
origin  of,  37 
changes  in  pressure,  25 
chemical  characteristics,  26 
color,  24 

in  disease,  24 
drugs  in,  32 
fibroblasts  in,  38 
function,  18,  19 
general  considerations,  24 
globulin  in,  Nissl's  demonstra- 
tion, 28 
leukocytes  in,  36 
lymphocytes  in,  32 
physical  properties,  24 
physiology,  18 

protein  in,  methods  for  deter- 
mination, 26 
Kaplan's  method,  29 
Lange  method,  28 
Noguchi  method,  28 
Nonne-Apelt    reaction, 

27 
Pandy  reaction,  30 
Phase  I  reaction,  27 
Ross-Jones  method,  27 
Sippy-Moody   method, 

28 
Zaloziecki  reaction,  30 
reaction,  26 
transparency,  25 
tubercle  bacilli  in,  search  for, 

45 
type,  negative,  of  cerebrospi- 
nal syphilis,  157 
positive,     of     cerebrospinal 
syphilis,  155,  167,  170 
urotropin  in,  32 
Wassermann  reaction  on,  78 
withdrawing  of,  17,  19.      See 
also  Lumbar  puncture. 
meningitis,  epidemic,  85 
syphilis,  152 
22 


Cerebrospinal    syphilis,    acellular 
type,  159,  170 
general  paresis  and,  relation, 
156 
serologic     differentiation, 
190 
interrelationship,  165 
gummatous  form,  170 
influence  of  treatment  on  se- 
rology and  course  of,  160 
negative  spinal  fluid  type,  157 
Plaut  type,  157,  167,  168,  170 
positive  spinal  fluid  type,  155, 

167,  170 
resume,  167 

taboparesis  and,  serologic  dif- 
ferentiation, 190 
Chancres  cephaliques,  198 
Chemical   characteristics  of  cere- 
brospinal fluid,  26 
Chemicals  and  reagents  for  Was- 
sermann reaction,  56 
point  to  be  observed  in  introduc- 
tion, 207 
Chemotherapy,  principle  involved 

in,  205 
Chills  and  fever  after  injection  of 

salvarsan,  249 
Chorea,  114 
Coal-tar  psychosis,  125 
Color  of  cerebrospinal  fluid,  24 

in  disease,  24 
Combined  sclerosis,  101 
Complement  deviation,  phenome- 
non of,  47-50 
for  Wassermann  reaction,  57 
place  of  origin,  58 
Compulsion  neuroses,  113 
Constitutional  inferiority,  117 
Controls  in  Wassermann  reaction, 

75 
Cord,  spinal,  diseases  of,  100 
Crisis,  penile,  in  tabes,  145 
Cytology,  32 

Dementia  prapcox,  123 
presenile,  121       * 


338 


INDEX 


Dementia,  senile,  121 

Depression,  anxiety,  123 

Detre  and  Brezovsky's  modifica- 
tion of  Wassermann  reaction,  74 

Diabetes,  129 

Diabetic  intoxications,  129 
neuritis,  111 

Diarrhea  after  injection  of  salvar- 
san,  249 

Dichlorphenylarsenious  acid,  204 

Dioxydiamidoarsenobenzol,  205 

Dioxydiaminoarsenobenzol,  204 

Diphtheric  meningitis,  86 
neuritis,  111 

Dosage  of  salvarsan,  213 

Drugs  in  cerebrospinal  fluid,  32 

Dystrophia  adiposo-genitalis,  116 

Eclampsia,  130 

Eclamptic  intoxications,  130 

Ehrlich's    conception    of    chemo- 
therapy, 205,  206 
theory  of  immunity,  206 

Ellis  and  Swift's  combined  method 
of  injecting  salvarsan,  241 

Endarteritic  form  of  cerebral  syph- 
ilis, 170,  171 

Epidemic  cerebrospinal  meningitis, 
85 

Epilepsies,  113 

Erythrochromia,  171 

Erythromelalgia,  116 

Exophthalmic  goiter,  116 

Extraneous  intoxications,  131 

Family  idiocy,  amaurotic,  99 

Fetal  liver  extract,  watery  luetic, 
preparation  of,  for  Wassermann 
reaction,  68 

Fever  and  chills  after  injection  of 
salvarasn,  249 

Fibroblasts  in  cerebrospinal  fluid, 
38 

Fox-Trimble  apparatus  for  intra- 
venous injection  of  salvarsan, 
218 


French  conception  of  serologic  pro- 
gression in  general  paresis,  183 
method  of  counting  cells  in  cere- 
brospinal fluid,  39 
Friedreich's  disease,  102 
Fuchs-Rosenthal    counting   cham- 
ber for  cerebrospinal  fluid,  41,  42 

Gangrene,  symmetric,  115 

Gas,  illuminating,  poisoning  from, 
131 

Gattermann's    table    for    amino- 
nitrogen  calculation,  259 

Gengou-Bordet  phenomenon,  47 

Gigantism,  116 

Globulin    in    cerebrospinal    fluid, 
Nissl's  demonstration,  28 

Glutaminic  acid,  254 

Goiter,  exophthalmic,  116 

Gold  chlorid  curve,  184 

in  general  paresis,  186,  187 
in  taboparesis,  186 

Gonococcic  meningitis,  86 

Gummatous  form  of  cerebral  syph- 
ilis, 170 

Headache  after  injection  of  sal- 
varsan, 248 
Hecht's   modification   of   Wasser- 
mann reaction,  74 
Hematomyelia,  106 
Hemolytic  amboceptor  for  Wasser- 
mann reaction,  prepara- 
tion and  properties,  59 
standardization,  62 
Hemorrhage,  cerebral,  95 
Hemorrhagic  pachymeningitis,  in- 
ternal, 94 
Hereditary  ataxia,  102 
Herpes  zoster,  111 
Herxheimer   reaction    after   injec- 
tion of  salvarsan,  250 
reaction  due  to  arsenic  intol- 
erance and,  differentiation, 
252 
Hydrocephalus,  99 
angioneuroticus,  99 


INDEX 


339 


Hyperlymphocytic  type  of  tabes, 

134,  135,  150 
Hypertrophic     laminated      spinal 

meningitis,  94 
Hysteria,  111 

Icteric  intoxications,  130 
Icterus,  130 
Idiocy,  120 

amaurotic  family,  99 
Illuminating  gas,  poisoning  from, 

131 
Imbecility,  120 

Immunity,  Ehrlich's  theory,  206 
Infantile  paralysis,  103 
Influenza  meningitis,  86 
Insanity,  manic  depressive,  122 
Instruments  for  intravenous  injec- 
tion of  salvarsan,  215 

for  Wassermann  reaction,  54 
Intensive  intravenous  injection  of 
salvarsan,  242 

method  of  treatment  with  neosal- 
varsan,  246 
Internal  secretion,  disorders  of,  116 
Intoxications,  128 

atropin,  131 

carbon  monoxid,  131 

diabetic,  129 

eclamptic,  130 

extraneous,  131 

icteric,  130 

lead,  131 

manganese,  131 

mercury,  131 

metabolic,  128 

uremic,  128 
Intramuscular  injection  of  salvar- 
san, 214 
reaction  from,  247,  248 
Intraspinous  and  intravenous  in- 
jection of  salvarsan,  239 
Intravenous  and  intraspinous  in- 
jection of  salvarsan,  239 

injection  of  salvarsan,  213 

Fox-Trimble  apparatus  for, 
218 


Intravenous    injection  of    salvar- 
san,      instruments       re- 
quired, 215 
intensive,  242 
Iversen-Wolbarst  apparatus 

for,  216 
Kaplan's  apparatus  for,  216 
reaction  from,  247,  248 
Iversen-Wolbarst     apparatus     for 
intravenous  injection  of  salvar- 
san, 219 

Jaundice,  130 
Juvenile  paresis,  119,  191 
tabes,  142,  150 

Kaplan's  apparatus  for  intraven- 
ous injection  of  salvarsan,  216 
reaction  for  determining  protein 
in  cerebrospinal  fluid,  29 

Klausner's  reaction  in  syphilis,  75 

Korsakoff  syndrome,  124 

Lange    reaction    for    determining 

protein  in  cerebrospinal  fluid,  28 
Lateral  sclerosis,  100 
Lead  intoxication,  131 

neuritis,  110 

psychosis,  124 
Les  enfants  arrieres,  119 
Leucin,  254 
Leukocytes  in  cerebrospinal  fluid, 

36 
Literature,  264-334 
Little's  disease,  100 
Liver  extract,  watery  luetic  fetal, 

preparation  of,  for  Wassermann 

reaction,  68 
Locomotor  ataxia,  132.     See  also 

Tabes  dorsalis. 
Low-power  amboceptor,  64 
Lues.     See  Syphilis. 
Luetic  fetal  liver  extract,  watery, 

preparation  of,  for  Wassermann 

reaction,  68 
Lumbar  puncture,  19 

after-care  of  patient,  22 


340 


INDEX 


Lumbar    puncture,    contraindica- 
tions, 19 

disposal  of  obtained  fluid,  22 

history  of,  17 

indications,  19 

phenomena  attending,  21 

preparation  of  patient,  19 

technic,  20 
Lymphocytes  in  cerebrospinal  fluid, 
32 

Manganese  intoxications,  131 
Manic  depressive  insanity,  122 
Marsh  test  for  detection  of  arsenic, 

237 
Meier    and    Porges'    reaction    in 

syphilis,  74 
Meningeal  affections,  85 
Meningismus,  91 

Meningitic  form  of  cerebral  syph- 
ilis, 170 
Meningitis,      cerebrospinal,      epi- 
demic, 85 

diphtheric,  86 

gonococcic,  86 

influenza,  86 

micotic,  with  demonstrable  bac- 
teria in  fluid,  85 

non-micotic,  92 

of  otic  origin,  89 

paratyphoid,  87 

pneumococcic,  89 

secondary,  92 

serosa,  92 

sine  meningitide,  91 

spinal,    hypertrophic  laminated, 
94 

staphylococcus,  90 

streptococcic,  90 

tuberculous,  87 

typhoid,  87 
Mental  diseases  of  luetic  origin,  132 

of  non-luetic  etiology,  84 
Mercury  intoxication,  131 
Metabolic  intoxications,  128 
Micotic   meningitis   with   demon- 
strable bacteria  in  fluid,  85 


Monosymptomatic  tabes,  143 
Morphin  psychosis,  125 
Muencke's  distilling  apparatus,  220 
Multiple  neuritis,  109 

sclerosis,  105 
Muscular  atrophy,  progressive,  105 

neurospinal  form,  105 

spinal  form,  104 
Myasthenia  gravis,  117 
Myelitis,  acute,  102 
Myxedema,  116 

Nageotte's  counting  chamber  for 

cerebrospinal  fluid,  39,  40 
Nausea  after  injection  of  salvarsan, 

248 
Negative  spinal  fluid  type  of  cere- 
brospinal syphilis,  157 
type  of  tabes,  136,  150,  151 
absolute,  138,  150 
relative,  137,  138 
Neosalvarsan,  208 

intensive  method  of  treatment 

with,  246 
preparation  of,  222 
properties  of,  209 
Nerve  affections,  109 
Nervous  diseases,  functional,  111 
of  luetic  origin,  132 
of  non-luetic  etiology,  84 
Neurasthenia,  112 
Neuritis,  alcoholic,  109 
diabetic,  111 
diphtheric,  111 
lead,  110 
Neuroses,  anxiety,  113 

compulsion,  113 
Nissl's  demonstration  of  globulin 
in  cerebrospinal  fluid,  28 
method  of  counting  cells  in  cere- 
brospinal fluid,  39 
Noguchi's    method    of    preparing 
acetone  insoluble  antigen,  69 
modification  of  Wassermann  re- 
action, 73 
reaction  for  determining  protein 
in  cerebrospinal  fluid,  28 


INDEX 


341 


Nonne-Apelt  reaction  for  determin- 
ing protein  in  cerebrospinal  fluid, 
27 

Otic  meningitis,  89 

Pachymeningitis     hsemorrhagica 

interna,  94 
Pandy    reaction    for    determining 
protein  in  cerebrospinal  fluid,  29 
Para-amido-phenyl-sodium     arsen- 
ate, 201 
Paralysis  agitans,  114 
congenital,  spastic,  100 
infantile,  103 
spinal  spastic,  100 
Paramyoclonus  multiplex,  114 
Paranoid  states,  123 
Paraparesis,  senile  spastic,  101 
Paratyphoid  meningitis,  87 
Paresis,  general,  173 

alcoholic  psychosis   and,  dif- 
ferentiation, 197 
cerebral  syphilis  and,  relation, 

171 
cerebrospinal     syphilis     and, 
serologic       differentia- 
tion, 190 
relation,  156,  165 
French  conception  of  serologic 

progression  in,  183 
full-fledged  type,  178 
gold  chlorid  curve  in,  186,  187 
influence  of  treatment  on  se- 
rology of,  193 
post-traumatic  psychoses  and, 

differentiation,  196 
pseudoparesis  and,  differentia- 
tion, 197 
resume  and  remarks,  195 
step-ladder  curve  in,  186 
tabes  and,    serologic    interre- 
lationship between,  149 
theory    of    Wassermann    fast 

phenomenon,  176 
tissue  staining  in,  technic,  175 
Treponema  pallidum  in,  173 


Paresis,  general,  Treponema  pal- 
lidum in,  173 
detection,  174 
distribution,  174 
juvenile,  119,  191 
Parkinson's  disease,  114 
Patient,  after-care  of,  after  injec- 
tion of  salvarsan,  228 
preparation  of,  for  injection  of 
salvarsan,  222 
Penile  crisis  in  tabes,  145 
Phase  I  reaction  for  determining 
protein  in  cerebrospinal  fluid,  27 
Phenomenon,   Bordet-Gengou,   47 
of  complement  deviation,  47-50 
Wassermann  fast,  theory  of,  in 
general  paresis,  176 
Plasma  cells  of  Alzheimer  in  cere- 
brospinal fluid,  35 
Plaut  type  of  cerebrospinal  syph- 
ilis, 157,  167,  168,  170 
Pleocytosis,  93 
Pneumococcic  meningitis,  89 
Poliomyelitis,  anterior,  103 
Porges    and    Meier's   reaction    in 

syphilis,  74 
Porges  and  Salomon's  reaction  in 

syphilis,  75 
Positive  spinal  fluid  type  of  cere- 
brospinal ayphilis,  155,  167,  170 
Postpartum    infections,    infective 

exhaustive  psychoses  in,  126 
Post-salvarsan  manifestations,  247 
Presenile  dementia,  121 
Progressive  muscular  atrophy,  105 
neurospinal  form,  105 
spinal  form,  104 
Protein     in     cerebrospinal     fluid, 
methods    for    deter- 
mination, 26 
Kaplan's  method,  29 
Lange  method,  28 
Noguchi  method,  28 
Nonne-Apelt    reaction, 

27 
Pandy  method,  30 
Phase  I  reaction,  27 


342 


INDEX 


Protein    in    cerebrospinal    fluid, 
methods    for    deter- 
mination, Ross-Jones 
method,  27 
Sippy-Moody   method, 

28 
Zaloziecki  reaction,  30 
Pseudomeningitis,  91 
Pseudoparesis,  general  paresis  and, 

differentiation,  197 
Pseudotabes  alcoholica,  109 
Psychasthenia,  113 
Psychoneuroses,  113 
Psychoses,  117 

accompanying  organic  brain  dis- 
eases, 122 
alcoholic,    general   paresis   and, 

differentiation,  197 
coal-tar,  125 
functional,  122 

infective  exhaustive,  in  postpar- 
tum infections,  126 
in  tuberculosis,  125 
in  typhoid  fever,  125 
lead,  124 
morphin,  125 
organic,  121 
post-traumatic,   general    paresis 

and,  differentiation,  196 
toxic,  123 
traumatic,  126 
Puncture,  lumbar,  19 

after-care  of  patient,  22 
contraindications,  19 
disposal  of  obtained  fluid,  22 
history  of,  17 
indications,  19 
phenomena  attending,  21 
preparation  of  patient,  19 
technic,  20 
of  vein,  technic,  50-53 
Quincke's,  19.     See  also  Lumbar 
puncture. 

Quincke  set,  20 

Quincke's  puncture,  19.    See  also 
Lumbar  puncture. 


Rachicentesis,    19.         See  also 

Lumbar  puncture. 
Raynaud's  disease,  115 
Reaction,  Bauer's,  73 

biologic,  for  detection  of  arsenic, 
236 

Boas',  74 

Browning's,  74 

Detre  and  Brezovsky,  74 

due  to  arsenic  intolerance,  Herx- 
heimer  reaction  and,  differen- 
tiation, 252 

gold  chlorid,  in  general  paresis, 
186,  187 
in  taboparesis,  186 

Hecht's,  74 

Herxheimer,    after   injection   of 
salvarsan,  250 
reaction  due  to  arsenic  intoler- 
ance and,  differentiation,  252 

Kaplan's,  for  determining  pro- 
tein in  cerebrospinal  fluid,  29 

Klausner's,  in  syphilis,  75 

Lange,  for  determining  protein 
in  cerebrospinal  fluid,  28 

Marsh,  for  detection  of  arsenic, 
237 

Nonne-Apelt,  for  determining 
protein  in  cerebrospinal  fluid, 
27 

Noguchi,  73 
for    determining    protein    in 
cerebrospinal  fluid,  28 

of  cerebrospinal  fluid,  26 

Pandy,  for  determining  protein 
in  cerebrospinal  fluid,  30 

Phase  I,  for  determining  protein 
in  cerebrospinal  fluid,  27 

Porges  and  Meier's,  in  syphilis, 
74 

Porges  and  Salomon's,  in  syph- 
ilis, 75 

Ross-Jones,  for  determining  pro- 
tein in  cerebrospinal  fluid,  27 

Sippy-Moody,  for  determining 
protein  in  cerebrospinal  fluid, 
28 


INDEX 


343 


Reaction,  Stern's,  74 
Tschernogouboff,  74 
Wassermann.     See  also  Wasser- 
mann reaction. 
Zaloziecki,  for  determining  pro- 
tein in  cerebrospinal  fluid,  30 
Reagents  for  Wassermann  reaction, 
56 
technic  of  preparation,  57 
Reagin,  50 
Rondoni  and  Sachs'  formula  for 

antigen,  72 
Ross-Jones  reaction  for  determin- 
ing protein  in  cerebrospinal  fluid, 
27 

Sachs  and  Rondoni's  formula  for 

antigen,  72 
Salomon  and  Porges'  reaction  in 

syphilis,  75 
Salvarsan,  201 

after-care  of  patient  after  injec- 
tion of,  228 

aortic  aneurysm  as  contraindi- 
cation to  use,  234 

combined  intravenous  and  intra- 
spinous  injection,  239 

contraindications,  231 

development  of,  201 

dosage  of,  213 

early  methods  and  results,  210 

effects  accompanying  injection, 
227 

fate  of,  in  organism,  235 

history  and  development,  201 

indications  for,  229 

injection  of,  213 

after-care  of  patient,  228 
chills  and  fever  after,  249 
diarrhea  after,  249 
effects  accompanying,  227 
headache  after,  248 
Herxheimer  reaction  after,  250 
nausea  after,  248 
preparation  of  patient  for,  222 
skin  manifestations  after,  249 
technic,  223 


Salvarsan,   injection  of,  vomiting 
after,  248 
intensive  intravenous  injection, 

242 
intramuscular  injection,  214 
reaction  from,  247,  248 
intravenous  injection,  213 

Fox-Trimble  apparatus  for, 

218 
instruments  required,  215 
intensive,  242 
Iversen-Wolbarst  apparatus 

for,  219 
Kaplan's  apparatus  for,  216 
reaction  from,  247,  248 
preparation  of,  219 
acid  solution,  210 
alkaline  solution,  210 
neutral  emulsion,  211 
oil  and  paraffin  mixtures,  212 
patient  for  injection,  222 
properties  of,  208 
technic  of  injection,  223 
therapeutic  use,  201 
toxic  effects,  234 
water  error  in  use  of,  234 
Scleroderma,  115 

Sclerosis,  amyotrophic  lateral,  104 
combined,  101 
lateral,  100 
multiple,  105 
Secretion,    internal,    disorders   of, 

116 
Senile  dementia,  121 

spastic  paraparesis,  101 
Serologist,  attitude  of,  on  Wasser- 
mann reaction,  78 
Serology,  47 

Serum,  amino-nitrogen  content  of, 
253 
preparation  of  apparatus  for 

use,  255 
rationale,  253 
technic,  255 
testing  for,  258 
non-leutic,  amino-nitrogen  con- 
tent of,  262 


344 


INDEX 


Sippy-Moody  reaction  for  deter- 
mining protein  in  cerebrospinal 
fluid,  28 

Skin  manifestations  after  injection 
of  salvarsan,  249 

Softening,  cerebral,  98 

Spasmophilic  states,  113 

Spastic  paralysis,  congenital,  100 
spinal,  100 
paraparesis,  senile,  101 

Spinal  column,  tumors  of,  109 
cord,  diseases  of,  100 

tumors  of,  107 
fluid.        See  also  Cerebrospinal 

fluid. 
meningitis,    hypertrophic    lami- 
nated, 94 
spastic  paralysis,  100 
syphilis,  172 

Spondylitis  tuberculosa,  107 

Staining  tissue,  technic  of,  in  gen- 
eral paresis,  175 

Standardization  of  an  extract  to  be 
used  as  antigen  in  Wassermann 
reaction,  71 
of  anti-sheep  amboceptor,  62 
together  with  antigen  and 
normal  serum,  63 
of  hemolytic  amboceptor,  62 

Staphylococcus  meningitis,  90 

Step-ladder  curve  in  general  pare- 
sis, 186 

Stern's  modification  of  Wasser- 
mann reaction,  74 

Streptococcic  meningitis,  90 

St.  Vitus'  dance,  114 

Subarachnoid  space,  18 

Swift  and  Ellis'  combined  method 
of  injecting  salvarsan,  241 

Symmetric  gangrene,  115 

Syndrome,  Korsakoff,  124 

Syphilis,  arsacetin  in,  202 
atoxyl  in,  201 
Bauer's  reaction  in,  73 
Boas'  reaction  in,  74 
Browning's  reaction  in,  74 
cerebral,  170 


!  Syphilis,     cerebral,      endarteritic 
form,  171 
general  paresis  and,  relation, 

171 
gummatous  form,  170 
meningitic  form,  170 
cerebrospinal,  152 

acellular  type,  159,  170 
general  paresis  and,  relation, 
156 
serologic     differentiation, 
190 
interrelationship,  165 
influence  of  treatment  on  se- 
rology and  course  of,  160 
negative    spinal    fluid    type, 

157 
Plaut    type,    157,    167,    168, 

170 
positive  spinal  fluid  type,  155, 

167,  170 
resume,  167 

taboparesis  and,  serologic  dif- 
ferentiation, 190 
Detre  and  Brezovsky's  reaction 

in,  74 
early,  197 

significance  of,  197 
Hecht's  reaction  in,  74 
Klausner's  reaction  in,  75 
Noguchi  reaction  in,  73 
of  brain,  170 
Porges  and  Meier's  reaction  in, 

74 
Porges  and  Salomon's  reaction 

in,  75 
salvarsan  in,  201.     See  also  Sal- 
varsan. 
spinal,  172 

Stern's  reaction  in,  74 
Tschernogouboff's    reaction    in, 

74 
Wassermann    reaction    in,    47. 
See  also  Wassermann  reaction. 
Syphilitic   serum,    amino-nitrogen 

content  of,  261 
Syringomyelia,  108 


INDEX 


345 


Tabes  dorsalis,  132 

general  paresis  and,  serologic 
interrelationship     between, 
149 
hyperlymphocytic  type,    134, 

135,  150 
influence  of  therapy  and  se- 
rology on  clinical  course  of, 
145 
juvenile,  142,  150 
monosyrnptomatic,  143 
negative  type,  136,  150,  151 
absolute,  138,  150 
relative,  137,  138,  150 
penile  crisis  in,  145 
resume,  150 
usual     serologic     type,     134, 

150 
Wassermann  fast,  138,  150 
Taboparesis,  149 

cerebrospinal  syphilis  and,  sero- 
logic differentiation,  190 
gold  chlorid  curve  in,  186 
Technology,  17 
Test.     See  Reaction. 
Tetrabromarsenophenol,  204 
Tetrachlorarsenophenol,  204 
Therapia  sterilisans  magna,    207, 

213,  214 
Therapy,  influence  of,  on  serology 
and     clinical    course    of 
tabes,  145 
and  course  of  cerebrospinal 

syphilis,  160 
of  general  paresis,  193 
Thrombosis,  cerebral,  96 
Tissue  staining,  technic  of,  in  gen- 
eral paresis,  175 
Toujours  en  retard,  119 
Toxic  effects  of  salvarsan,  234 

psychoses,  123 
Transparency  of  cerebrospinal  fluid, 

25 
Traumatic  psychosis,  126 
Treatment,  influence  of,  on  serol- 
ogy and  clinical  course  of  tabes, 
145 


Treatment,  influence  of,  on  serol- 
ogy and  course  of  cere- 
brospinal syphilis,  160 
of  general  paresis,  193 
Treponema    pallidum    in    general 
paresis,  173 
detection,  174 
distribution,  174 
Trimble-Fox  apparatus  for  intra- 
venous  injection    of   salvarsan, 
218 
Tschernogouboff's  modification  of 

Wassermann  reaction,  74 
Tubercle  bacilli   in    cerebrospinal 

fluid,  search  for,  45 
Tuberculosis,  infective   exhaustive 

psychoses  in,  125 
Tuberculous  meningitis,  87 
Tumors,  cerebral,  96 
of  spinal  column,  109 
cord,  107 
Typhoid  fever,  infective  exhaustive 
psychoses  in,  125 
meningitis,  87 
Tyrosin,  254 

Uremia,  128 

Uremic  intoxications,  128 

Urotropin  in  cerebrospinal  fluid,  32 

Vasotrophic  disorders,  115 
Vein,  puncture  of,  technic,  50-53 
Vomiting  after  injection  of  salvar- 
san, 248 

Wassermann    fast    phenomenon, 
theory  of,  in  general  paresis, 
176 
tabes,  138,  150 
reaction,  alcoholic  tissue  antigens 
in,  69 
antigen    in,    inhibitory    sub- 
stances used  as,  72 
preparation  and  properties, 
65 
attitude  of  serologist  and,  79 
Bauer' 6  modification,  73 


346 


INDEX 


Wassermann  reaction,  Boas'  modi- 
fication, 74 

Browning's  modification,  74 

chemicals  for,  56 

collecting  blood  for,  53 

complement  for,  57 

controls  in,  75 

Detre  and  Brezovsky's  modi- 
fication, 74 

development  of,  47 

Hecht's  modification,  74 

hemolytic  amboceptor  for, 
preparation  and  properties, 
59 

history  of,  47 

inhibitory  substances  used  as 
antigens  in,  72 

instruments  for,  54 

modifications  of,  73 

Noguchi's  modification,  73 

on  cerebrospinal  fluid,  78 

performance  of,  77 

rationale  and  specificity,  56 

reagents  for,  56 
technic  of  preparation,  57 


Wassermann  reaction,  specificity, 
56 
standardization  of  an  extract 

to  be  used  as  antigen,  71 
Stern's  modification,  74 
Tschernogouboff's      modifica- 
tion, 74 
watery  luetic  fetal  liver  extract 
for,  preparation  of,  68 
Water  error  in  use  of  salvarsan,  234 
reaction  of  Klausner  in  syphilis, 
75 
Watery  luetic  fetal  liver  extract, 
preparation  of,  for  Wassermann 
reaction,  69 
Wolbarst-Iversen     apparatus     for 
intravenous  injection  of  salvar- 
san, 219 

Xanthochromia,  24,  171 

Zaloziecki  reaction  for  determin- 
ing protein  in  cerebrospinal 
fluid,  30 


SAUNDERS*    BOOKS 

SUHGERY 

and 

ANATOMY 


W.  B.  SAUNDERS   COMPANY 

WEST  WASHINGTON  SQUARE  PHILADELPHIA 

o.  HENRIETTA  STREET     COVENT  GARDEN,  LONDON 


Crile   and   Lower's 
Anoci-Associ&tion 

Anoci=Association.  By  George  W.  Crile,  M.  D.,  F.  R.  C.  S.,  Pro- 
fessor of  Surgery,  and  William  E.  Lower,  M.  D.,  Assistant  Professor 
of  Genito-Urinary  Surgery,  Western  Reserve  University.  Octavo  of 
275  pages,  illustrated. 

JUST  OUT— EXTREMELY  IMPORTANT 

Anoci-association  is  the  prevention  of  postoperative  shock — not  its  treatment. 
Anoci-association  robs  surgery  of  its  harshness,  diminishes  postoperative  mortality, 
lessens  postoperative  complications  (shock,  nausea,  vomiting,  gas  pains,  back- 
ache, nephritis,  pneumonia,  etc.).  You  get  here,  first  of  all,  a  monograph  on 
shock — its  kinetic  theory,  its  histologic  and  clinical  pathology,  and  its  treatment. 
Then  follow  chapters  on  the  principles  of  anoci-association;  the  technic  oi  its  appli- 
cation in  the  administration  of  the  anesthetic  in  abdominal  operations  (gall-bladder, 
gastric,  intestinal  operations,  herniotomy,  perineal  operations,  abdominal  infec- 
tions, appendicitis,  pelvic  infections);  in  gynecologic  operations  (tumors,  suspension 
of  uterus,  pus  tubes);  in  genito-urinary  work  (bladder,  kidney,  prostate);  in  opera- 
tions for  cancer  of  the  breast,  rectum,  stomach,  uterus,  larynx,  and  tongue;  in 
exophthalmic  goiter  operations;  in  operations  on  the  brain  and  the  extremities 
(amputations,  osteotomy,  accidents).  Then  come  chapters  on  anoci-association  and 
blood-firessuT-e,  the  relation  to  postoperative  morbidity  and  mortality,  and  the 
technic  of  nitrous-oxid-oxygen  anesthesia  with  details  for  equipping  a  hospital 
plant  for  the  manufacture  of  nitrous  oxid. 


SAUNDERS'    BOOKS    ON 


The  New  Keen's   Surgery 

Surgery:  Its  Principles  and  Practice.  Written  by  8 1  eminent 
specialists.  Edited  by  W.  W.  Keen,  M.  D.,  LL.D.,  Hon.  F.R.C.S.,  Eng. 
and  Edin.,  Emeritus  Professor  of  the  Principles  of  Surgery  and  of 
Clinical  Surgery  at  the  Jefferson  Medical  College.  Six  octavos  of  1050 
pages  each,  containing  3100  original  illustrations,  157  in  colors.  Per 
volume  :  Cloth,  $7.00  net ;  Half  Morocco,  $8.00  net. 

VOLUME  VI  GIVES   YOU  THE   NEWEST  SURGERY 

ALL  THE  ADVANTAGES  OF  A  REVISION  AT  ONE-FIFTH  THE  COST 

We  have  issued  a  Volume  VI  of  "  Keen  " — the  volume  of  the  newest  surgery- 
In  this,  way  you  get  all  the  advantages  of  a  complete  and  thorough  revision  at  but 
one-fifth  the  cost.  It  makes  Keen' s  Surgery  the  best,  the  most  up-to-date  surgery 
on  the  market. 

In  this  sixth  volume  you  get  the  newest  surgery — both  general  and  special — 
from  the  pens  of  those  same  international  authorities  who  have  made  the  success 
of  Keen's  Surgery  world-wide.  Each  man  has  searched  for  the  new,  the  really 
useful,  in  his  particular  field,  and  he  gives  it  to  you  here.  Here  you  get  the 
newest  surgery,  and  fully  illustrated.  Then,  further,  you  get  a  complete  index  to 
the  entire  six  volumes,  covering  125  pages,  but  so  arranged  that  reference  to  it  is 
extremely  easy.  If  you  want  the  newest  surgery,  you  must  turn  to  the  new 
«'  Keen  ' '  for  it. 


Bryan's   Surgery 

Principles  of  Surgery.  By  W.  A.  Bryan,  M.  D.,  Professor  of  Sur- 
gery and  Clinical  Surgery  at  Vanderbilt  University,  Nashville.  Octavo 
of  677  pages,  with  224  original  illustrations.  Cloth,  $4.00  net. 

JUST   ISSUED 

Dr.  Bryan  here  gives  you  facts,  accurately  and  concisely  stated,  without  which 
no  modern  practitioner  can  do  modern  work.  He  discredits  many  fallacious 
ideas,  giving  you  facts  instead.  He  shows  you  in  a  most  practical  way  the  rela- 
tions between  surgical  pathology  and  the  resultant  symptomatology,  and  points 
out  the  influence  such  information  has  on  treatment. 

Dr.  A.  Vander  Veer,  Albany  Medical  College 

"  It  comes  to  us  full  of  new  ideas.  So  much  that  is  clear  and  concise  has  been  added  that 
it  is  fascinating  to  study  the  work.     It  is  bound  to  receive  a  hearty  welcome." 


SURGERY  AND  ANATOMY 


Hornsby   and   Schmidt's 
The  Modern  Hospital 

The  Modern  Hospital.  Its  Inspiration ;  Its  Construction ;  Its 
Equipment;  Its  Mangement.  By  John  A.  Hornsby,  M.  D.,  Secre- 
tary, Hospital  Section,  American  Medical  Association;  and  Richard 
E.  Schmidt,  Architect.  Large  octavo  of  644  pages,  with  207  illus- 
trations. Cloth,  $7.00  net;  Half  Morocco,  $8.50  net. 
HOSPITAL  EFFICIENCY 

"Hornsby  and  Schmidt"  tells  you  just  exactly  how  to  plan,  construct,  equip, 
and  manage  a  hospital  in  all  its  departments,  giving  you  every  detail.  It  gives 
you  exact  data  regarding  heating,  ventilating,  plumbing,  refrigerating,  etc. — and 
the  costs.  It  tells  you  how  to  equip  a  modern  hospital  with  modern  appliances. 
It  tells  you  what  you  need  in  the  operating  room,  the  wards,  the  private  rooms, 
the  dining  room,  the  kitchen — every  division  of  hospital  housekeeping.  It  gives 
you  the  duties  of  the  directors,  the  superintendent,  the  various  staffs,  their  relations 
to  each  other.  It  tells  you  all  about  nurses'  training-schools — their  management, 
curriculum,  rules,  regulations,  etc.  It  gives  you  hundreds  of  valuable  points  on 
the  business  management  of  hospitals — large  and  small. 

Howell  Wright,  Superintendent  City  Hospital,  Cleveland 

"  To  me  the  book  is  invaluable.  I  have  a  copy  on  my  desk  and  scarcely  a  day  passes 
but  what  I  consult  it  and  find  what  I  want." 


Allen's  Local  Anesthesia 

Local  Anesthesia.  By  Carroll  W.  Allen,  M.  D.,  Instructor  in 
Clinical  Surgery  at  Tulane  University  of  Louisiana.  Octavo  of  625 
pages,  illustrated. 

JUST  READY 

This  is  a  complete  work  on  this  subject.  You  get  the  history  of  local 
anesthesia,  a  chapter  on  nerves  and  sensation,  giving  particular  attention  to  pain 
— what  it  is  and  its  psychic  control.  Then  comes  a  chapter  on  osmosis  and 
diffusion.  Each  local  anesthetic  is  taken  up  in  detail,  giving  very  special  atten- 
tion to  cocain  and  novocain,  pointing  out  the  action  on  the  nervous  system,  the 
value  of  adrenalin,  paralysis  caused  by  cocain  anesthesia,  control  of  toxicity. 
You  get  Crile's  method  of  administering  adrenalin  and  salt  solution,  the  exact 
way  to  produce  the  intradermal  wheal,  to  pinch  the  flesh  for  the  insertion  of  the 
needle — all  shown  you  step  by  step.  You  get  full  discussions  of  paraneural, 
intraneural,  and  spinal  analgesia,  intravenous  and  intra-arterial  anesthesia,  and 
Hackenbuck's  regional  anesthesia  by  circumferential  injections.  You  get  indica- 
tions, contraindications,  an  article  on  anoci-association,  with  Crile's  technic  for 
producing  anesthesia.  Then  the  production  of  local  anesthesia  in  the  various 
regions  is  taken  up  in  detail.  Spinal  analgesia  and  epidural  injections  are  con- 
sidered in  a  monogragh  of  45  pages.     There  is  a  large  section  on  dental  anesthesia. 


SAUNDERS'   BOOKS  ON 


Cotton's 

Dislocations    and    Joint    Fractures 

Dislocations  and  Joint  Fractures.     By  Frederic  Jay  Cotton,  M.  D., 

First  Assistant  Surgeon  to  the  Boston  City  Hospital.  Octavo  of  654 
pages,  with  1201  original  illustrations.  Cloth,  $6.00  net;  Half  Morocco, 
#7.50  net. 

TWO  PRINTINGS  IN  EIGHT  MONTHS 

Dr.  Cotton's  clinical  and  teaching  experience  in  this  field  has  especially  fitted 
him  to  write  a  practical  work  on  this  subject.  He  has  written  a  book  clear  and 
definite  in  style,  systematic  in  presentation,  and  accurate  in  statement.  The 
illustrations  possess  the  feature  of  showing  just  those  points  the  author  wishes  to 
emphasize.     This  is  made  possible  because  the  author  is  himself  the  artist. 

Boston  Medical  and  Surgical  journal 

"  The  work  is  delightful,  spirited,  scholarly,  and  original,  and  is  not  only  a  book  of  refer- 
ence, but  a  book  for  casual  reading.     It  brings  the  subject  up  to  date,  a  feat  long  neglected." 


Murphy's  Famous  Clinics 


Clinics  of  John  B.  Murphy,  M  .D.,  at  Mercy  Hospital,  Chicago. 

Issued  serially,  one  number  every  other  month  (six  numbers  a  year). 
Each  issue  about  200  octavo  pages,  illustrated.  Per  year:  $8.00;. 
Cloth,  $12.00.     Sold  only  by  the  calendar  year. 

DOWN-TO-THE-MINUTE  SURGERY 

This  is  just  the  work  you  have  been  waiting  for — a  permanent  record  of  the 
teachings  of  this  great  surgeon.  These  are  not  students'  clinics,  but  delivered  at 
Mercy  Hospital,  Chicago,  for  physicians  only.  They  are  postgraduate  clinics. 
These  Clinics  are  published  just  as  delivered  by  Dr.  Murphy,  an  expert  stenogra- 
pher taking  down  everything  Dr.  Murphy  says  and  does.  In  this  way  these 
Clinics  retain  all  that  individual  force  and  charm  so  characteristic  of  the  clinical 
teaching  of  this  distinguished  surgeon.  But  the  most  vital  point  about  these 
Clinics  is  that  they  are  absolutely  fresh.  They  give  you  a  continuous  postgraduate 
course  right  in  your  own  office  with  John  B.  Murphy  as  your  teacher.  They  have 
been  called  "  The  Practitioner's  Text-book." 


SURGER  Y  AND  ANA  TO  MY 


Crandon  and  Ehrenfried's 
Surgical    After-treatment 

Surgical  After-treatment.  A  Manual  of  the  Conduct  of  Surgical 
Convalescence.  By  L.  R.  G.  Crandon,  M.  D.,  Assistant  in  Surgery, 
and  Albert  Ehrenfried,  M.  D.,  Assistant  in  Anatomy,  Harvard  Medi- 
cal School.  Octavo  of  831  pages,  with  265  original  illustrations. 
Cloth,  $6.00  net ;  Half  Morocco,  $7.50  net. 

THE  NEW  (2d)   EDITION,  PRACTICALLY  REWRITTEN 

This  work  tells  how  best  to  manage  all  problems  and  emergencies  of  surgical 
convalescence  from  recovery-room  to  discharge.  It  gives  all  the  details  com- 
pletely, definitely,  yet  concisely,  and  does  not  refer  the  reader  to  some  other 
work  perhaps  not  then  available.  The  post-operative  conduct  of  all  operations 
is  given,  arranged  alphabetically  by  regions.  A  special  feature  is  the  elaborate 
chapter  on  Vaccine  Therapy,  Immunization  by  Inoculation  and  Specific  Sera, 
by  Dr.  George  P.  Sanborn,  a  disciple  of  Sir  A.  E.  Wright.     The  text  is  illustrated. 

The  Therapeutic  Gazette 

"The  book  is  one  which  can  be  read  with  much  profit  by  the  active  surgeon  and  will  be 
generally  commended  by  him." 


Papers  from  the   Mayo   Clinic 

Collected  Papers  by  the  Staff  of  St.  Mary's  Hospital,  Mayo  Clinic. 

By  William  J.  Mayo,  M.  D.,  Charles  H.  Mayo,  M.  D.,  and  their  Asso- 
ciates at  St.  Mary's  Hospital,  Rochester,  Minn.  Papers  of  1905- 1909, 
Papers  of  1910,  Papers  of  191 1,  Papers  of  1912,  Papers  of  1913.  Each 
an  octavo  of  about  800  pages,  illustrated.     Per  volume  :  Cloth,  $5.50  net. 

PAPERS  OF  1913  NOW  READY 

These  volumes  give  you  all  the  clinical  teachings,  all  the  important  papers  of 
W.  J.  and  C.  H.  Mayo  and  their  associates  at  St.  Mary's  Hospital.  They  give  you 
the  advances  in  operative  technic,  in  methods  of  diagnosis  as  developed  at  this 
great  clinic.  This  new  volume,  although  called  the  IQ13  volume,  gives  you  many 
papers  that  did  not  appear  until  well  into  IQ14,  quite  a  few  being  scheduled  for  as 
late  as  May  and  June.     You  should  add  this  volume  to  your  Mayo  files. 

Bulletin  Medical  and  Chirurgical  Faculty  of  Maryland 

"  Much  of  the  work  done  at  the  Mayo  Clinic  and  recorded  in  these  papers  has  been  epoch- 
making  in  character.  *   *    *    Represents  a  most  substantial  block  of  modern  surgical  progress." 

A  Collection  of  Papers  (published  previous  to  1909).  By 
William  J.  Mayo,  M.  D.,  and  Charles  H.  Mayo,  M.  D.  Two  octavos 
of  525  pages  each,  illustrated.     Per  set :   Cloth,  $10.00  net. 


SAUNDERS'   BOOKS  ON 


Mumford's 
Practice  of   Surgery 

The  Practice  of  Surgery.  By  James  G.  Mumford,  M.  D.,  In- 
structor in  Surgery,  Harvard  Medical  School.  Octavo  of  1015  pages, 
with  682  illustrations.     Cloth,  $7.00  net;   Half  Morocco,  $8.50  net. 

JUST  OUT— NEW  (2d)  EDITION 

This,  as  its  title  implies,  is  a  work  on  the  clinical  side  of  surgery — surgery  as 
it  is  seen  at  the  bedside,  in  the  accident  ward,  and  in  the  operating  room.  It  ex- 
presses the  matured  outgrowth  of  twenty  years  of  active  hospital  and  private 
surgical  practice,  together  with  the  experience  gained  from  clinical  teaching,  class- 
room discussions,  and  lectures. 
John  B.  Murphy,  M.D.*,  Professor  of Surgery \  Northwestern  Medical  School,  Chicago. 

"  This  work  truly  represents  Dr.  Mumford's  intellectual  capacity  and  scope,  and  presents 
in  a  terse,  forceful,  yet  pleasing  manner,  the  live  surgical  topics  of  the  day.  It  is  in  every  par- 
ticular up  to  date,  and  shows  that  rare  quality  of  accentuating  the  essential  and  omitting  the 
unnecessary." 

DaCosta's  Modern  Surgery 

Modern  Surgery — General  and  Operative.  By  John  Chalmers 
DaCosta,  M.  D.,  Samuel  D.  Gross  Professor  of  Surgery,  Jefferson 
Medical  College,  Philadelphia.  Octavo  of  1 5 1 5  pages,  with  1085  illus- 
trations. Cloth,  $6.00  net;  Half  Morocco,  $7.50  net. 

JUST  READY— NEW  (7th)  EDITION 

A  surgery,  to  be  of  the  maximum  value,  must  be  up  to  date,  must  be  com- 
plete, must  have  behind  its  statements  the  sure  authority  of  experience,  must.be  so 
arranged  that  it  can  be  consulted  quickly ;  in  a  word,  it  must  be  practical  and 
dependable.  Such  a  surgery  is  DaCosta's.  Always  an  excellent  work,  for  this 
edition  it  has  been  very  materially  improved  by  the  addition  of  new  matter  to  the 
extent  of  over  250  pages  and  by  a  most  thorough  revision  of  the  old  matter. 
Many  old  cuts  have  been  replaced  by  new  ones,  and  nearly  1 50  additional  illus- 
trations have  been  added. 


Rudolph  Matas,  M.  D.,  Professor  of  Surgery,  Tulane  University  of  Louisiana. 

"  This  edition  is  destined  to  rank  as  high  as  its  predecessors,  which  have  placed  the  learned 
author  in  the  fore  of  text-book  writers.  The  more  I  scrutinize  its  pages  the  more  I  admire  the 
marvelous  capacity  of  the  author  to  compress  so  much  knowledge  in  so  small  a  space." 


&&RGERY  AND  ANATOMY 


Scudder's 
Treatment  of  Fractures 

WITH  NOTES  ON  DISLOCATIONS 

The  Treatment  of  Fractures :  with  Notes  on  a  few  Common 
Dislocations.  By  Charles  L.  Scudder,  M.D.,  Surgeon  to  the  Massa- 
chusetts General  Hospital,  Boston.  Octavo  of  708  pages,  with  994 
original  illustrations.  Polished  Buckram,  $6.00  net;  Half  Morocco, 
#7.50  net. 

THE  NEW  (7th)  EDITION,  ENLARGED 
OVER  33,500  COPIES 


The  fact  that  this  work  has  attained  a  seventh  edition  indicates  its  practical 
value.  In  this  edition  Dr.  Scudder  has  made  numerous  additions  throughout 
the  text,  and  has  added  many  new  illustrations,  greatly  enhancing  the  value  of 
the  work.  In  every  way  this  new  edition  reflects  the  very  latest  advances  in  the 
treatment  of  fractures. 

J.  F.  Binnie,  M.D.,  University  of  Kansas 

"  Scudder's  Fractures  is  the  most  successful  book  on  the  subject  that  has  ever  been  pub. 
lished.     I  keep  it  at  hand  regularly." 


Scudder's  Tumors  of  the  Jaws 

Tumors  of  the  Jaws.  By  Charles  L.  Scudder,  M.  D.,  Surgeon 
to  the  Massachusetts  General  Hospital,  Boston.  Octavo  of  395  pages, 
with  353  illustrations,  6  in  colors.  Cloth,  $6.00  net;  Half  Morocco, 
$7.50  net. 

WITH  NEW  ILLUSTRATIONS 

Dr.  Scudder  in  this  book  tells  you  how  to  determine  in  each  case  the  form  of 
new  growth  present  and  then  points  out  the  best  treatment.  As  the  tendency  of 
malignant  disease  of  the  jaws  is  to  grow  into  the  accessory  sinuses  and  toward 
the  base  of  the  skull,  an  intimate  knowledge  of  the  anatomy  of  these  sinuses  is 
essential.  Dr.  Scudder  has  included,  therefore,  sufficient  anatomy  and  a  number 
of  illustrations  of  an  anatomic  nature.  Whether  general  practitioner  or  surgeon, 
you  need  this  new  book  because  it  gives  you  just  the  information  you  want. 


SAUNDERS*  BOOKS  ON 


Sisson's 
Veterinary   Anatomy 

Text=Book  of  Veterinary  Anatomy.     By  Septimus  Sisson,  S.  B., 

V.  S.,  Professor  of  Comparative  Anatomy  in  Ohio  State  University. 
Octavo  volume  of  826  pages,  with  588  illustrations,  mostly  original 
and  many  in  colors.     Cloth,  $7.00  net;  Half  Morocco,  $8.50  net. 

WITH  SUPERB  ILLUSTRATIONS 

This  is  a  clear  and  concise  statement  of  the  essential  facts  regarding  the 
structure  of  the  principal  domesticated  animals,  containing  many  hitherto  unpub- 
lished data  resulting  from  the  detailed  study  of  formalin-hardened  subjects  and 
frozen  sections.  Nearly  all  of  the  illustrations  are  original,  the  majority  being 
reproduced  from  photographs,  and  colors  frequently  used.  The  terminology  has 
been  carefully  revised  with  reference  to  the  B.  N.  A.  and  the  nomenclature 
adopted  by  European  comparative  anatomists. 

Boston  Medical  and  Surgical  Journal 

"  It  is  not  amiss  to  say  that  the  work  ranks  with  the  best.  A  marked  advance  in  English 
veterinary  literature,  upon  which  student  and  practitioner  may  well  congratulate  themselves 
and  no  medical  school  can  afford  to  be  without.  It  is  an  exhaustive  gross  anatomy  of  the 
horse,  ox,  pig,  and  dog,  including  the  splanchnology  of  the  sheep." 

Gant  on  Constipation  and 
Intestinal  Obstruction 

Constipation  and  Intestinal  Obstruction.  By  Samuel  G.  Gant, 
M.  D.,  Professor  of  Diseases  of  the  Rectum  and  Anus,  New  York 
Post-Graduate  Medical  School  and  Hospital.  Octavo  of  559  pages, 
with  250  original  illustrations.  Cloth,  $6.00  net ;  Half  Morocco,  $7.50  net. 

INCLUDING  RECTUM  AND  ANUS 

In  this  work  the  consideration  given  to  the  medical  treatment  of  constipation 
is  unusually  extensive.  The  practitioner  will  find  of  great  assistance  the  chapter 
devoted  to  formulas.  The  descriptions  of  the  operative  procedures  are  concise, 
yet  fully  explicit. 

The  Proctologist 

' '  Were  the  profession  better  posted  on  the  contents  of  this  book  there  would 
be  less  suffering  from  the  ill  effects  of  constipation.  We  congratulate  the  author 
on  this  most  complete  book." 


SURGER  Y  AND  ANA  TOMY 


Kelly  &  Noble's  Gynecology 
and  Abdominal  Surgery 

Gynecology  and  Abdominal  Surgery.  Edited  by  Howard  A. 
Kelly,  M.D.,  Professor  of  Gynecology  in  Johns  Hopkins  University; 
and  Charles  P.  Noble,  M.D.,  formerly  Clinical  Professor  of  Gyne- 
cology in  the  Woman's  Medical  College,  Philadelphia.  Two  imperial 
octavo  volumes  of  950  pages  each,  containing  880  original  illustrations, 
some  in  colors.  Per  volume:  Cloth,  $8.00  net;  Half  Morocco,  $9.50 
net. 

WITH  880  ILLUSTRATIONS— TRANSLATED  INTO  SPANISH 

This  work  possesses  a  number  of  valuable  features  not  to  be  found  in  any 
other  publication  covering  the  same  fields.  It  contains  a  chapter  upon  the  bac- 
teriology and  one  upon  the  pathology  of  gynecology,  and  a  large  chapter  devoted 
entirely  to  medical  gynecology ,  written  especially  for  the  physician  engaged  in 
general  practice.  Abdominal  stirgery  proper,  as  distinct  from  gynecology,  is 
fully  treated,  embracing  operations  upon  the  stomach,  intestines,  liver,  bile-ducts, 
pancreas,  spleen,  kidneys,  ureter,  bladder,  and  peritoneum. 

American  Journal  of  Medical  Sciences 

"  It  is  needless  to  say  that  the  work  has  been  thoroughly  done ;  the  names  of  the  authors 
and  editors  would  guarantee  this,  but  much  maybe  said  in  praise  of  the  method  of  presentation, 
and  attention  may  be  called  to  the  inclusion  of  matter  not  to  be  found  elsewhere.'' 


Bickham's    Operative   Surgery 

A  Text=Book  of  Operative  Surgery.  By  Warren  Stone  Bickham, 
M.D.,  of  New  York.  Octavo  of  1200  pages,  with  854  original  illustra- 
tions.    Cloth,  #6.50  net ;  Half  Morocco,  $8.00  net. 

THE   NEW  (3d)    EDITION 
This  work  completely  covers  the  surgical  anatomy  and  operative  technic  in- 
volved in  the  operations  of  general  surgery.     The  practicability  of  the  work  is 
particularly  emphasized  in  the  854  magnificent  illustrations. 

Boston  Medical  and  Surgical  Journal 

"The  book  is  a  valuable  contribution  to  the  literature  of  operative  surgery.  It  represents 
a  vast  amount  of  careful  work  and  technical  knowledge  on  the  part  of  the  author.  For  the  sur- 
geon in  active  practice  or  the  instructor  of  surgery  it  is  an  unusually  good  review  of  the  subject." 


lo  SAUNDERS'  BOOKS  ON 

Eisendrath's 
Surgical  Diagnosis 

A  Text-Book  of  Surgical  Diagnosis.  By  Daniel  N.  Eisendrath, 
M.D.,  Professor  of  Surgery  in  the  College  of  Physicians  and  Surgeons, 
Chicago.  Octavo  of  885  pages,  with  574  entirely  new  and  original 
text-illustrations  and  some  colored  plates.  Cloth,  $6.50  net;  Half 
Morocco,  $8.00  net. 

THE  NEW  (2d)  EDITION 

Of  first  importance  in  every  surgical  condition  is  a  correct  diagnosis,  for  upon 
this  depends  the  treatment  to  be  pursued  ;  and  the  two — diagnosis  and  treatment — 
constitute  the  most  practical  part  of  practical  surgery.  Dr.  Eisendrath  takes  up 
each  disease  and  injury  amenable  to  surgical  treatment,  and  sets  forth  the  means 
of  correct  diagnosis  in  a  systematic  and  comprehensive  way.  Definite  directions 
as  to  methods  of  examination  are  presented  clearly  and  concisely,  providing  for 
all  contingencies  that  might  arise  in  any  given  case.  Each  illustration  indi- 
cates precisely  how  to  diagnose  the  condition  considered. 

Surgery,  Gynecology,  and  Obstetrics 

"The  book  is  one  which  is  well  adapted  to  the  uses  of  the  practising  surgeon  who  desires 
information  concisely  and  accurately  given.  .  .  .  Nothing  of  diagnostic  importance  is  omitted, 
yet  the  author  does  not  run  into  endless  detail." 


Eisendrath's  Clinical  Anatomy 

A  Text=Book  of  Clinical  Anatomy.  By  Daniel  N.  Eisendrath, 
A.B.,  M.D.,  Professor  of  Surgery  in  the  College  of  Physicians  and 
Surgeons,  Chicago.  Octavo  of  535  pages,  illustrated.  Cloth,  $5.00 
net;  Half  Morocco,  $6.50  net. 

THE   NEW  (2d)  EDITION 

This  new  anatomy  discusses  the  subject  from  the  clinical  standpoint.  A  por- 
tion of  each  chapter  is  devoted  to  the  examination  of  the  living  through  palpation 
and  marking  of  surface  outlines  of  landmarks,  vessels,  nerves,  thoracic  and 
abdominal  viscera.  The  illustrations  are  from  new  and  original  drawings  and 
photographs.     This  edition  has  been  carefully  revised. 

Medical  Record,  New  York 

"  A  special  recommendation  for  the  figures  is  that  they  are  mostly  original  and  were 
made  for  the  purpose  in  view.  The  sections  of  joints  and  trunks  are  those  of  formalinized 
cadavers  and  are  unimpeachable  in  accuracy." 


SURGER  Y  AND  ANA  TOMY  1 1 


Fenger  Memorial  Volumes 

Fenger  Memorial  Volumes.  Edited  by  Ludvig  Hektoen,  M.  D., 
Professor  of  Pathology,  Rush  Medical  College,  Chicago.  Two  octavos 
of  5  25  pages  each.  Per  set:  Cloth,  $15.00  net ;  Half  Morocco,  $18.00  net. 

LIMITED  EDITION 

These  handsome  volumes  consist  of  all  the  important  papers  written  by  the  late 
Christian  Fenger,  for  many  years  professor  of  surgery  at  Rush  Medical  College, 
Chicago.  Not  only  the  papers  published  in  English  are  included,  but  also  those 
which  originally  appeared  in  Danish,  German,  and  French. 

The  name  of  Christian  Fenger  typifies  thoroughness,  extreme  care,  deep  re- 
search, and  sound  judgment.  His  contributions  to  the  advancement  of  the  world's 
surgical  knowledge  are  indeed  as  valuable  and  interesting  reading  to-day  as  at 
the  time  of  their  original  publication.  They  are  pregnant  with  suggestions. 
Fenger' s  literary  prolificacy  may  be  judged  from  this  memorial  volume — over 
1000  pages. 

Sobotta  and  McMurrich's 
Human  Anatomy 

Atlas  and  Text- Book  of  Human  Anatomy.  In  Three  Volumes.  By 
J.  Sobotta,  M.D.,  of  Wurzburg.  Edited,  with  additions,  by  J.  Playfair 
McMurrich,  A.  M.,  Ph.  D.,  Professor  of  Anatomy,  University  of 
Toronto,  Canada.  Three  large  quartos,  each  containing  about  250 
pages  of  text  and  over  300  illustrations,  mostly  in  colors.  Per  volume : 
Cloth,  $6.00  net ;  Half  Morocco,  $7.50  net. 

Edward  Martin,  M.D.,  Professor  of  Clinical  Surgery,  University  of  Pennsylvania 

"  This  is  a  piece  of  bookmaking  which  is  truly  admirable,  with  plates  and  text  so  well 
chosen  and  so  clear  that  the  work  is  most  useful  to  the  practising  surgeon." 


Campbell's  Surgical  Anatomy 

A  Text-Book  of  Surgical  Anatomy.  By  William  Francis  Camp- 
bell, M.  D.,  Professor  of  Anatomy,  Long  Island  College  Hospital. 
Octavo  of  675  pages,  with  319  original  illustrations.     Cloth,  $5.00  net. 

SECOND  EDITION 

This  is  in  the  fullest  sense  an  applied  anatomy — an  anatomy  that  will  be  of 
inestimable  value  to  the  surgeon  because  only  those  facts  are  discussed  and  only 
those  structures  and  regions  emphasized  that  have  a  peculiar  interest  to  him. 

Boston  Medical  and  Surgical  Journal 

"  The  author  has  an  excellent  command  of  his  subject,  and  treats  it  with  the  freedom  and 
the  conviction  of  the  experienced  anatomist.     He  is  also  an  admirable  clinician." 


SAUNDERS   BOOKS  ON 


Moynihan's  Duodenal  Ulcer 

Duodenal  Ulcer.  By  B.  G.  A.  Moynihan,  M.S.  (London),  F.R.C.S., 
Leeds,  England.  Octavo  of  486  pages,  illustrated.  Cloth,  $5.00  net; 
Half  Morocco,  $6.50  net. 

THE  NEW  (2d)  EDITION 

For  this  edition  the  work  has  been  entirely  reset  and  brought  up  to  date.  All 
the  cases  operated  upon  since  the  appearance  of  the  first  edition  have  been  in- 
cluded and  a  new  chapter  added  on  Jejunal  and  Gastro-jejunal  Ulcers. 


Moynihan's  Abdominal  Operations 

Abdominal  Operations.     By  B.  G.  A.  Moynihan,  M.  S.  (London), 

F.  R.  C.  S.,  Leeds,  England.     Octavo,  beautifully  illustrated. 

THE  NEW  (3d)  EDITION— PREPARING 

Edward  Martin,  M.  D.,  University  of  Pennsylvania. 

"It  is  a  wonderfully  good  book.     He  has  achieved  complete  success  in  illustrating,  both 
by  words  and  pictures,  the  best  technic  of  the  abdominal  operations  now  commonly  performed.' 


Moynihan  on  Gall-stones 

GalUStones  and  Their  Surgical  Treatment. — By  B.  G.  A.  Moyni- 
han, M.  S.  (London),  F.  R.  C.  S.,  Leeds,  England.  Octavo  of  45  8  pages, 
illustrated.     Cloth,  $5.00  net;  Half  Morocco,  $6.50  net. 

THE  NEW  (2d)  EDITION 

Mr.  Moynihan,  in  revising  his  book,  has  made  many  additions  to  the  text,  so 
as  to  include  the  most  recent  advances.  Especial  attention  has  been  given  to  a 
detailed  description  of  the  early  symptoms  in  cholelithiasis,  enabling  a  diagnosis 
to  be  made  in  the  stage  in  which  surgical  treatment  can  be  most  safely  adopted. 

British  Medical  Journal 

"  He  expresses  his  views  with  admirable  clearness,  and  he  supports  them  by  a  large  num- 
ber of  clinical  examples,  which  will  be  much  prized  by  those  who  know  the  difficult  problems 
and  tasks  which  gall-stone  surgery  not  infrequently  presents." 


Dannreuther's  Minor  and  Emergency  Surgery 

Minor  and  Emergency  Surgery.  By  Walter  T.  Dannreuther,  M.D.,  Surgeon 
to  St.  Elizabeth's  Hospital  and  to  St.  Bartholomew's  Clinic,  New  York  City.  l2mo  of  225 
pages,  illustrated.      Cloth,  5 1. 25  net. 

ILLUSTRATED 

Dr.  Dannreuther  emphasizes  just  those  points  most  necessary  in  emergency  work,  giving  numerous  hints 
and  suggestions  that  cannot  help  hut  be  of  great  value  to  you  in  emergency  work  and  in  minor  operations. 


SURGER  Y  AND  ANA  TOMY  13 

Schultze  and  Stewart's  Topographic  Anatomy 

Atlas  and  Text=Book  of  Topographic  and  Applied  Anatomy.  By  Prof. 
Dr.  O.  Schultze,  of  Wiirzburg.  Edited,  with  additions,  by  George  D. 
Stewart,  M.D.,  Professor  of  Anatomy  and  Clinical  Surgery,  University 
and  Bellevue  Hospital  Medical  College,  N.  Y.  Large  quarto  of  189  pages, 
with  25  colored  figures  on  22  colored  lithographic  plates,  and  89  text-cuts,  60 
in  colors.     Cloth,  $5,50  net. 

Griffith's  Hand-Book  of  Surgery 

A  Manual  of  Surgery.  By  Frederic  R.  Griffith,  M.  D.,  Surgeon  to  the 
Bellevue  Dispensary,  New  York  City.  i2mo  of  579  pages,  with  417  illus- 
trations. Flexible  leather,  $2.00  net. 

Keen's  Addresses  and  Other  Papers 

Addresses  and  Other  Papers.  Delivered  by  William  W.  Keen,  M.  D., 
LL.D.,  F.  R.  C.  S.  (Hon.),  Professor  of  the  Principles  of  Surgery  and  of  Clin- 
ical Surgery,  Jefferson  Medical  College,  Philadelphia.  Octavo  volume  of 
441  pages,  illustrated.  Cloth,  $3.75  net. 

Keen  on  the  Surgery  of  Typhoid 

The  Surgical  Complications  and  Sequels  of  Typhoid  Fever.     By  Wm.  W. 

Keen,  M.D.,  LL.D.,  F.R.C.S.  (Hon.),  Professor  of  the  Principles  of  Surgery 
and  of  Clinical  Surgery,  Jefferson  Medical  College,  Philadelphia,  etc, 
Octavo  volume  of  386  pages,  illustrated.  Cloth,  $3.00  net. 

Gould's  Operations  on  Intestines  and  Stomach 

The  Technic  of  Operations  Upon  the  Intestines  and  Stomach.  By  Al- 
fred H.  Gould,  M.  D.,  of  Boston.  Large  octavo,  with  190  original  illustra- 
tions, some  in  colors.      Cloth,  $5.00  net;   Half  Morocco,  $6.50  net. .. 

Bier's  Hyperemia  second  Edition 

Bier's  Hyperemic  Treatment  in  Surgery,  Medicine,  and  the  Specialties  : 
A  Manual  of  its  Practical  Application.  By  Willy  Meyer,  M.  D.,  Professor 
of  Surgery  at  the  New  York  Post-Graduate  Medical  School  and  Hospital  ;  and 
Prof.  Dr.  Victor  Schmieden,  Assistant  to  Prof.  Bier,  University  of  Berlin, 
Germany.      Octavo  of  280  pages,  with  original  illustrations.      Cloth,  $3.00  net. 

"  We  commend  this  work  to  all  those  who  are  interested  in  the  treatment  of  infections,  either  acute  or 
chonic,  for  it  is  the  only  authoritative  treatise  we  have  in  the  English  language." — New  York  State 
Journal  of  Medicine. 

Morris*  Dawn  of  the  Fourth  Era  in  Surgery 

Dawn  of  the  Fourth  Era  in  Surgery   and   Other   Articles.     By 

Robert  T.  Morris,  M.  D.,  Professor  of  Surgery,  New  York  Post-Graduate 
Medical  School  and  Hospital.      i2mo  of  145  pages,  illustrated.     $1.25  net. 


14  SAUNDERS'   BOOKS    ON 

Haynes'  Anatomy 

A  Manual  of  Anatomy.  By  Irving  S.  Haynes,  M.D.,  Professor  of  Prac- 
tical Anatomy,  Cornell  University  Medical  College.  Octavo,  680  pages, 
with  42  diagrams  and  134  full-page  half-tones.  Cloth,  $2.50  net. 

American  Pocket  Dictionary  New  (8th)  Edition 

The  American  Pocket  Medical  Dictionary.     Edited  by  W.  A.  Newman 

Dorland,  A.  M.,  M.  D.,  Editor  "American  Illustrated  Medical  Dictionary." 
677  pages.  Full  leather,  limp,  with  gold  edges,  $1.00  net;  with  patent 
thumb  index,  $1.25  net. 

McClellan's  Art  Anatomy 

Anatomy  in  its  Relation  to  Art.  By  George  McClellan,  M.  D.,  Professor 
of  Anatomy,  Pennsylvania  Academy  of  the  Fine  Arts.  Quarto  volume,  9  by 
12^-2  inches,  with  338  original  drawings  and  photographs,  and  260  pages  of 
text.      Dark  blue  vellum,  $10.00  net;   Half  Russia,  $12.50  net. 

Fowler's  Surgery  in  Two  volumes 

A  Treatise  on  Surgery.  By  George  R.  Fowler,  M.  D.,  Emeritus  Pro- 
fessor of  Surgery,  New  York  Polyclinic.  Two  imperial  octavos  of  725  pages 
each,  with  888  original  text-illustrations  and  4  colored  plates.  Per  set : 
Cloth,  $15.00  net;  Half  Morocco,  $18.00  net. 

International  Text-Book  of  Surgery  second  Edition 

The  International  Text=Book  of  Surgery.  In  two  volumes.  By  Ameri- 
can and  British  authors.  Edited  by  J.  Collins  Warren,  M.  D.,  LL.  D., 
F.  R.  C.  S.  (Hon.),  .Professor  of  Surgery,  Harvard  Medical  School ;  and  A. 
Pearce  Gould,  M.  S.,  F.  R.  C.  S.,  of  London,  England.  Vol.  I.  :  General 
and  Operative  Surgery.  Royal  octavo,  975  pages,  461  illustrations,  9  full- 
page  colored  plates.  Vol.  II.  :  Special  or  Regional  Surgery.  Royal  octavo, 
1 122  pages,  499  illustrations,  and  8  full-page  colored  plates.  Per  volume  : 
Cloth,  $5.00  net ;  Half  Morocco,  $6.50  net. 

American  Text-Book  of  Surgery  Fourth  Edition 

American  Text=Book  of  Surgery.  Edited  by  W.  W.  Keen,  M.  D., 
LL.  D.,  Hon.  F.  R.  C.  S.,  Eng.  and  Edin.,  and  J.  William  White, 
M.  D.,  Ph.  D.  Octavo,  1363  pages,  551  text-cuts  and  39  colored  and 
half-tone  plates.     Cloth,  $7.00  net ;  Half  Morocco,  $8.50  net.  . 

Robson  and  Cammidge  on  the  Pancreas 

The  Pancreas :  Its  Surgery  and  Pathology.  By  A.  W.  Mayo  Robson, 
F.  R.  C.  S.,  of  London,  England;  and  P.  J.  Cammidge,  F.  R.  C.  S.,  of 
London,  England.  Octavo  of  546  pages,  illustrated.  Cloth,  $5.00  net; 
Half  Morocco,  $6. 50  net. 


S  UR  GERY  A  ND   A  NA  TOM\ .  15 

American  Illustrated  Dictionary  The  New  7th)  Edition 

The  American  Illustrated  Medical  Dictionary.  With  tables 
of  Arteries,  Muscles,  Nerves,  Veins,  etc.  ;  of  Bacilli,  Bacteria,  etc. ; 
Eponymic  Tables  of  Diseases,  Operations,  Stains,  Tests,  etc.  By  W.  A. 
Newman  Dorland,  M.D.  Large  octavo,  1107  pages.  Flexible  leather, 
$4.50   net;  with  thumb  index,  $5.00  net. 

Howard  A.  Kelly,  M.D.,  Prof essor  of  Gynecology ,  Johns  Hopkins  University,  Balti?nore. 

"Dr.  Dorland's  dictionary  is  admirable.  It  is  so  well  gotten  up  and  of  such  con- 
venient size.     No  errors  have  been  found  in  my  use  of  it." 

Golebiewski  and  Bailey's  Accident  Diseases 

Atlas  and  Epitome  of  Diseases  Caused  by  Accidents.      By  Dr. 

Ed.  Golebiewski,  of  Berlin.  Edited,  with  additions,  by  Pearce  Bailey, 
M.D.  Consulting  Neurologist  to  St.  Luke's  Hospital,  New  York  City. 
With  71  colored  figures  on  40  plates,  143  text-cuts,  and  549  pages  of 
text.  Cloth,  $4.00  net.     In  Saunders'  Hand- Atlas  Series. 

Helferich  and  Bloodgood  on  Fractures 

Atlas  and  Epitome  of  Traumatic    Fractures  and  Dislocations 

By  Prof.  Dr.  H.  Helferich,  of  Greifswald,  Prussia.  Edited,  with  ad- 
ditions, by  Joseph  C.  Bloodgood,  M.  D.,  Associate  in  Surgery,  Johns 
Hopkins  University,  Baltimore.  216  colored  figures  on  64  lithographic 
plates,  190  text-cuts,  and  353  pages  of  text.  Cloth,  $3.00  net.  In  Saun- 
ders'1 Atlas  Series. 

Sultan  and  Coley  on  Abdominal  Hernias 

Atlas  and  Epitome  of  Abdominal  Hernias.  By  Pr.  Dr.  G.  Sul- 
tan, of  Gottingen.  Edited,  with  additions,  by  Wm.  B.  Coley,  M.  D., 
Clinical  Lecturer  and  Instructor  in  Surgery,  Columbia  University,  New 
York.  119  illustrations,  36  in  colors,  and  277  pages  of  text.  Cloth, 
$3.00  net.     In  Saunders1  Hand- Atlas  Series. 

Warren's  Surgical  Pathology  ISn 

Surgical  Pathology  and  Therapeutics.  By  J.  Collins  Warren, 
M.D.,  LL.D.,  F.R.C.S.  (Hon.),  Professor  of  Surgery,  Harvard  Medical 
School.  Octavo,  873  pages;  136  illustrations,  t>Z  m  colors.  Cloth, 
$5.00  net;  Half  Morocco,  $6.50  net. 

Zuckerkandl  and  DaCosta's  Surgery  Id^on 

Atlas  and  Epitome  of  Operative  Surgery.  By  Dr.  O.  Zucker- 
kandl, of  Vienna.  Edited,  with  additions,  by  J.  Chalmers  DaCosta, 
M.D.,  Samuel  D.  Gross  Professor  of  Surgery,  Jefferson  Medical  Col- 
lege, Philadelphia.  40  colored  plates,  278  text-cuts,  and  410  pages  of 
text.      Cloth,  $3.50  net.     In  Saunders'  Atlas  Series. 


t6  SUR  GER  Y  AND  ANA  TO  MY 


Moore's  Orthopedic  Surgery 

A  Manual  of  Orthopedic  Surgery.     By  James  E.  Moore,  M.D.,  Professof 

of  Clinical  Surgery,  University  of  Minnesota,  College  of  Medicine  and  Surgery. 
Octavo  of  356  pages,  handsomely  illustrated.  Cloth,  $2.50  net. 

"  Ti!ie  b5°k  is  eminently  practical.  It  is  a  safe  guide  in  the  understanding  and  treatment  of 
orthopedic  cases.    Should  be  owned  by  every  surgeon  and  practitioner."— Annals  of  Surgery. 

Fowler's  Operating  Room  New  (3d)  Edition,  Reset 

The  Operating  Room  and  the  Patient.  By  Russell  S.  Fowler,  M.  D., 

Surgeon   to  the  German   Hospital,    Brooklyn,  New    York.     Octavo    of  611 

pages,  illustrated.  Cloth,  S3. 50  net. 

Dr.  Fowler  has  written  his  book  for  surgeons,  nurses  assisting  at  an  operation,  internes 
and  all  others  whose  duties  bring  them  into  the  operating  room.  It  contains  explicit 
directions  for  the  preparation  of  material,  instruments  needed,  position  of  patient,  etc. 
all  beautifully  illustrated. 

Nancrede's  Principles  of  Surgery      New  (2d)  Edition 

Lectures  on  the  Principles  of  Surgery.  By  Chas.  B.  Nancrede,  M.D., 
LL.D.,  Professor  of  Surgery  and  of  Clinical  Surgery,  University  of  Michigan, 
Ann  Arbor.     Octavo,  407  pages,  illustrated.  Cloth,  52. 5^  net. 

"  We  can  stronglj-  recommend  this  book  to  all  students  and  those  who  would  see  something 
of  the  scientific  foundation  upon  which  the  art  of  surgery  is  built." — Quarterly  Medical  Journal, 
Sheffield,  England. 

Nancrede's  Essentials  of  Anatomy,    seventh  Edition 

Essentials  of  Anatomy,  including  the  Anatomy  of  the  \Tiscera.  By  Chas. 
B.  Nancrede,  M.D.,  Professor  of  Surgery  and  of  Clinical  Surgery,  University 
of  Michigan,  Ann  Arbor.  Crown  octavo,  388  pages  ;  180  cuts.  With  an 
Appendix  containing  over  60  illustrations  of  the  osteology  of  the  body.  Based 
on  Gray 's  Anatomy '.  Cloth,  $1.00  net.     fn  Saunders*  Question  Comp ends. 

"  The  questions  have  been  wisely  selected,  and  the  answers  accurately  and  concisely  given."— 
University  Medical  Magazine. 

Martin's   Essentials  of   Surgery.     SevXvi£dtion 

Essentials  of  Surgery.  Containing  also  Venereal  Diseases,  Surgical  Land- 
marks, Minor  and  Operative  Surgery,  and  a  complete  description,  with  illus- 
trations, of  the  Handkerchief  and  Roller  Bandages.  By  Edward  Martin, 
A.M.,  M.D.,  Professor  of  Clinical  Surgery,  University  of  Pennsylvania,  etc. 
Crown  octavo,  338  pages,  illustrated.  With  an  Appendix  on  Antiseptic  Sur- 
gery, etc.  Cloth,  gi.oo  net.     In  Saunders1  Question  Compends. 

"Written  to  assist  the  student,  it  will  be  jf  undoubted  value  to  the  practitioner,  containing  as  it 
does  the  essence  of  surgical  work." — Boston  Medical  atid  Surgical  Journal. 

Martin's   Essentials  of  Minor  Surgery,  Band- 
aging,   and   Venereal    Diseases.       Seco£dm0fcnvised 

Essentials  of  Minor  Surgery,  Bandaging,  and  Venereal  Diseases.    By 

Edward  Martin,  A.M.,  M.D.,  Professor  of  Clinical  Surgery,  University  of 
Pennsylvania,  etc.   Crown  octavo,  166  pages,  with  78  illustrations. 

Cloth,  Si. 00  net.     I?i  Saunders'  Question  Compends 

"The  best  condensation  of  the  suDJects  of  which  it  treats  yet  placed  before  the  profession."— 
The  Medical  News,  Philadelphia. 


/2 


111 


1  ill 
IHllUllffll 

llllllnl  IllininnHlimUiBiin 


IBBl 

iHintmlm 

liiH 


in 
mm 

fin 


Ifflfltt 


llltl 


If 

mm 


Mm 

HI 


11 


Hi 
1 


if 


IP 

■r 


m 


in  mi 


liiiiiiiiiii 
lull 


I 

1 

illlllllllll   11 

it 


111 

11 
11 


1ft 


J  P 
lllillll 


